Altklausur Flashcards
In E.coli the co translational targeting depends on specific ribonucleoprotein complexes like
- SRP
- SecA
- SecB
SRP
The TAT-pathway
- allows the transmembrane transport of folded proteins
- allows the transport of protein complexes already loaded with cofactors
- is also present in plastids
- allows the transmembrane transport of folded proteins
- is also present in plastids
In E.coli the topogenesis of membrane proteins of the inner (plasma) membrane occurs in most cases
- co translational
- SecY-dependent
- YidC dependent but not SecY dependent
- co translational
Secretion of proteins via the Type IV system (T4SS) requires the hydrolysis of ATP in the
- cytoplasm
- periplasm
- the extracellular space
- cytoplasm
The formation of disulphide bounds in secretory proteins occurs in E. coli
- in the cytoplasm
- in the periplasm
- at the extraperiplasmic surface of the outer membrane
- periplasm
The lipidation of outer membrane proteins in bacteria occurs
- in the cytoplasm
- at the periplasmic surface of the plasma membrane
- at the periplasmic surface of the outer membrane
- in the cytoplasm
The import of proteins into the matrix of mitochondria requires a targeting signal
- that can form a amphipathic helix
- that contains positive charges
- that is enriched in leucines and isoleucines
The process uses
- GTP
- ATP
- PMF
as energy source.
- that can form a amphipathic helix
- ATP
beta-barrel proteins (e.g. porins) of the outer mitochondrial membranes are inserted
- directly from the cytoplasm
- using a pathway that crosses the inter membrane space
- using PMF as energy source
- using a pathway that crosses the inter membrane space
The inter membrane space
- has a redox potential that supports the formation of disulfide bounds
- has a redox potential that blocks the enzymatic reshuffling of disulfide bounds / requires enzymatic factors for the formation of disulfide bounds
- requires enzymatic factors for the formation of disulfide bounds
- has a redox potential that supports the formation of disulfide bounds
The inter membrane space
- has a redox potential that supports the formation of disulfide bounds
- has a redox potential that blocks the enzymatic reshuffling of disulfide bounds / requires enzymatic factors for the formation of disulfide bounds
- requires enzymatic factors for the formation of disulfide bounds
Complex plastids
- contain more than two internal membranes
- contain always two genomes of different evolutionary origin
- descend from eukaryotic plastid-containing protists
- contain more than two internal membranes
The vesicular transport between the ER and the Golgi apparatus requires the direct involvement of
- a COPII coat
- a COPI coat
- SNAREs
- COPI
- SNAREs
The KDEL-receptor usually transports
- soluble proteins from the ER to the Golgi
- membrane proteins from the ER to the Golgi
- Membrane proteins from the Golgi to the ER
if they have the KDEL motif at their C-terminus.
- membrane proteins from the Golgi to the ER
The import of activated sugars into the medial Golgi requires
- flippases and isoprenes
- antiporters
- aquaporins
- antiporters
The typical stack structure of the Mammalian Golgi is stabilized
- by a static matrix similar to the nuclear lattice
- through interactions between tethering factors which are also involved in membrane traffic through the Golgi and their regulators
- by membrane contact sites which also serve the lipid exchange between Golgi stacks
- through interactions between tethering factors which are also involved in membrane traffic through the Golgi and their regulators
The activation of preproproteinconvertases is triggered
- by cholesterol
- by the concentration of calcium ions
- by the pH
- by the concentration of calcium ions
Name the two currently discussed mechanisms explaining the formation of secretory storage vesicles
- cleavage by PC3 end-protease and PC2 end-protease
- cleavage by Carboxypeptidase
-> Disulfide bonds hold the rest together so that just A and B segment are left
Secretory vesicles form from the trans Golgi network, and they release their contents to the cell exterior by exocytosis in response to extracellular signals. The secreted product can be either a small molecule (such as histamine) or a protein (such as a hormone or digestive enzyme).
Presently there are three pathways discussed describing the behavior of synaptic vesicles. What are the typical properties that are under dispute for the respective pathway in brief?
KISS AND RUN
1) Docking
2) Priming
3) Fusion pore opening
4) Endocytosis
5) NT uptake
KISS AND STAY
1) NT uptake
2) Priming
3) Fusion pore opening
ENDOSOME RECYCLING MODEL
exocytosis/endocytosis cycle with a complete collapse of the vesicle with its target membrane
Phagocytosis depends on the reorganization of
- the cortical actin network
- the tubular spindles
- the Golgi apparatus
- the cortical actin network
The compartment specific release of ligands from their receptor in the different end-lysosomal compartment is usually regulated by
- the Zn concentration in the compartment
- the luminal pH of the compartment
- the binding of Ram proteins to the luminal domains of the receptor
- the binding of Ram proteins to the luminal domains of the receptor
The targeting signal of many enzymes to the lysosome in mammalian cells is
- mannose-6-phosphate
- glucose-1-phosphate
- the SKL-peptide
- mannose-6-phosphate
The degradation of lipid vesicles in lysosomes requires the destabilizing activity of
- glycosylated LAMPs
- the lipid LBPA
- activators presenting membrane lipids to lipases
- the lipid LBPA
A common feature of cytotoxic T-cells and mast cells is the existence of
- secretory lysosomes
- apical early endoscopes
- melanosomes
- secretory lysosomes
Downregulation of membrane receptors (e.g. EGF-receptor) requires
- ubiquitination of cytoplasmic receptor domains
- clathrine-dependent sorting to late endosomes
- ECRT-dependent sorting to internal vesicles of MVB
- ECRT dependent sorting to internal vesicles of MVB
Macroautophagy requires the involvement of
- ubiqutin-like protein tags
- membrane patches of the plasma membrane
- membrane patches of the inner nuclear membrane
- ubiquitin like protein tags
An important difference between microautophagy in comparison to macroautophagy is
- the lack of the formation of a double-membrane structure (phagophore)
- the involvement of lysosomal hydrolyses during digestion of the material
- the maximal size of objects that can be degraded by this process
- the lack of the formation of a double-membrane structure (Phagophore)
Describe briefly (one note for each!) the three currently discussed models, how exocytosis of secretory vesicles or secretory lysosomes may contribute to the repair of small holes on the plasma membrane or membrane ruptures.
SECRETORY LYSOSOMES / MVB
- hematopoietic cells (diverse content including exosomes and their content, acid hydrolyses and other proteins)
- acrosomes of sperm cells (procathepsin L; but also other models of its origin!)
- melanosomes (but also other models)
- secretion of morphogens in Drosophila?
EXOCYTOSIS OF CONVENTIONAL LYSOSOMES
- membrane repair (e.g. fibroblasts, muscle, stomach …)
- “defecation” mechanism by lysosomes in all cells?
- secretion is in both cases Ca2+-regulated
- machinery for exocytosis includes general but probably also cell-type specific factors
Name three pathways for lipid exchange between cellular compartments
- spontaneous exchange only fast for short or single-chain lipids (e.g. minutes for lysophosphatidylcholin)
- lipid transport using the membranous transport containers involved in protein transport
- lipid transfer proteins; also important for formation of lipid droplets
-> a) via Diffusion
-> b) via membrane contact sites - lipid exchange between leaflets of the same membrane occurs usually via flippases (ATP-dependent and ATP-independent)
Name the main steps during formation of the nucleus after mitosis of a typical mammalian cell
- Dephgosphorylation of components like INM, nuclear pore and lamin
- targeting of nucleocytoskeletal proteins and pre-pore forming nucleoporins to the chromosomal surface
- chromosome clustering removes cytoplasm from reassembling nucleus
- membrane recruitment (reticular ER and/or vesicles) and fusion by interaction of integral membrane proteins of the inner nuclear membrane (INM) with chromatin
- formation of ER sheets by enhanced recruitment of integral inner membrane proteins of the INM and of other sheet-forming components into these areas
- sealing of the envelop (annular fusion) by p97 and ESCRTIII at those sites, were MT (from the spindle) cross the nucleoplasm - cytoplasm borderline
- (final?) assembling of nuclear core complex
- transport of the bulk of laming into the nucleus via NPCs
- formation of the new lamina
The maturation of spliceosomal RNAs involves
- a transient presence of several RNA types in the cytoplasm
- base modifications for several RNA types in the Canal bodies
- base modifications for one type of RNA in the nucleolus
(- a transient presence of several RNA types in the cytoplasm)
- base modifications for one type of RNA in the nucleolus
Polyadenylation of RNA
- is a destabilizing motif in the bacteria
- is an enzymatic reaction in eukaryotes inly found during maturation of mRNAs
- is a prerequisite for export of most mRNAs from the nucleus
- is an enzymatic reaction in eukaryotes only found during maturation of mRNAs
Stress granules
- are cytoplasmic membrane surrounded organelles
- are storage sites for mRNA, ribosomal subunits and others during stress
- are sites of maturation of large ribosomal subunits
- are storage sites for mRNA, ribosomal subunits and others during stress
The nonsense-mediated decay (NMD) is a quality control step degrading compromised
- small ribosomal subunits
- tRNA
- mRNA
- mRNA
During post-translational transport across the plasma membrane of bacteria SecA
- directly recognizes and proof-reads the signal sequence
- moves the polypeptide through the SecYEG channel
- cleaves off the signal sequence.
Sec A needs for this
- ATP
- GTP
- PMF
- moves the polypeptide through the SecYEG-channel
- ATP
Combine the transporters with their correct function:
- Type V autotransporter
- Type III secretion system
- Tat-transporter
- Type I secretory system
- Needs SecYEG for the transport step across the plasma membrane
- can translocate substrates already folded in cytoplasm
- has an ATPase subunit located in the cytoplasm
- Type V autotransporter: needs SecYEG for the transport step across the plasma membrane
- Type III secretion system: has an ATPase subunit located in the cytoplasm
- Tat transporter: can translocate substrates already folded in the cytoplasm
- Type I secretory system: Needs SecYEG for the transport step across the plasma membrane?
In proteobacteria the linkage of disulphide bridges occurs usually (in the extracellular space / in the periplasmic space / in the cytoplasm). Finally, the excessive electrons are (usually / depending on the environmental conditions / never) transferred to oxygen. Eubacterial proteins are (often / rarely / never) modified via N-linked glycosylation. Proteins of the periplasm, which do not fold correctly, are usually (degraded by Clp-type proteases after backtranslocation into the cytoplasm / degraded by proteases in the periplasm / disposed by secretion across the outer membrane). The transport of lipids from the plasmamembrane (PM) to the outer membrane (OM) occurs (via vesicles / via Iipid transfer proteins, forming a street-like connection between the PM and the OM , via diffusion of soluble lipid-binding molecules across the periplasmic space).
- periplasmic space
- ?
- often
- degraded by proteases in the peri plasm
- via Lipid Transfer Proteins, forming a street like connection between the PM and the OM
(The Oxal protein of the inner membrane / protein complexes of the inter membrane space / the ToM-complex) is directly involved in the topogenesis of ß- barrel proteins of mitochondria.
Compared to the matrix, the inter membrane space of mitochondria is (oxidising / reducing / slightly acidic). The majority of proteins found in the stroma of plastids that are coded in the nucleus (are imported via the TOC / are imported via the TIC / contain a cleavable transit peptide)). Proteins with an N-linked glycosylation (have so far no been found in plastids I are frequently found with low abundance, due to the weak activity of an oligosaccharyltransferase in the thylakoid membrane / can be found in some rare cases indicating the existence of an import partway which goes across the endoplasmic reticulum).
According to the presently best-supported model (are all peroxisomal membrane proteins always imported directly from the cytoplasm into the peroxisome / are some membrane proteins able to enter the peroxisome via the endoplasmic reticulum / are all membrane proteins always entering the peroxisome via the endoplasmic reticulum).
- The Tom-complex
- reducing
- are imported via the TOC / are imported via the TIC
- can be found in some rare cases indicating the existence of an import pathway which goes across the endoplasmatic reticulum
- are some membrane proteins able to enter the peroxisome via the endoplasmic reticulum
Describe the transport cycte of the KDEL-receptor using the following terms: ER, Golgi, COPI, COPll, pH, cargo-binding, cargo’release, vesicle. Start with the ER
MAINTENANCE OF ER PROTEIN COMPOSITION
Two systems: Retention of proteins, retrieval of proteins
RETENTION
- due to direct or indirect association with cytoplasmic or nucleoplasmic elements (ribosomes, lamins etc) disfavoring entry into exit sites; indirect association could be driven by Ca2+ dependent interactions
-due to TMD with weak hydrophobicity
RETRIEVAL - NEEDS SORTING SIGNALS
- KDELcooh for luminal proteins (recognized by KDEL-receptor family)
- others (recognized by Erv41/46)
- signal in TM of proteins (recognized by Rer1)
- KKXXcooh for membrane proteins and
- XXRR- for Type II membrane proteins (both recognized directly by COPI-coat)
Secretory granules (SG) are formed at the (TGN / the sorting endosome / the endoplasmic reticulum) and regularly contain enzymes for (processing of pro- peptides / O-glycosylation / disulphide-bound reshuffling).
NSF (is an ATPase, which dissolved SNARE bundles / is a v-SNARE / is acting after the fusion pore has formed).
Essential factors for clathrine-mediated endocytosis are (Dynamins / SNARE- proteins I AP2l.
During micropinocytosis the membrane carriers (may be coated by clathrin / may be coated by calvin I may be without any detectable coat)’
- TGN = trans Golgi network
- O-glycosylation?
- is an ATPase, which dissolves SNARE bundles
- Dynamins
- may be coated by Clathrin
Explain the term “compensatory endocytosis”
- Endocytosis counterbalances exocytosis (compensatory endocytosis) recycling specific molecules (e.g. SNAREs) or large membrane areas (“excess retrieval”). It regulates the size of the PM and the cell shape.
- Endocytosis regulates the capacity of the PM for transport of molecules.
- Endocytosis regulates the capacity of the PM for transport of information (receptor down-regulation)
-> Endocytosis provides a platform for the integration of cellular signaling pathways
-> Endocyosis is involved in cell differentiation and embryonic development via clearance of receptors and joining structures from the PM - Pathogens and toxins usually enter the cell via endocytosis
The mannose-G-phosphatereceptor (transports acid hydrolases to the late endosome/lysosome / transports some soluble substrates destined for degradations from the extracellular space towards the late endosome/lysosome / guides defective channels from the plasmamembrane to the late endosome/lysosome).
Autophagy is upregulated (during starvation / in order to degrade intracellular pathogenes / during oocyte maturation in mammalia).
The membrane of inner vesicles of MVB are enriched in (Cardiolipine I Bis(monoacylglycero)phosphate / Ganglioside).
(Lysosoms / secretory granules / early (sorting) endosomes) provide the material for the formation and maturation of melanosomes.
- transports acid hydrolyses to the late endoscome lysosome
- during starvation / in order to degrade intracellular pathogens
- Cardiolipine
- Lysosomes
Name the two main mechanistic causes for the asymmetric distribution of membrane lipids at the eukaryotic plasma membrane
- Glycerophospholipids
- Sphingolipids + cholesterol -> lipid micro domains
- Bulk synthesis of lipids in the ER, Espresso. also at ER-Mito contact sites
- Mito synthesizes 45 % of its lipid content
Cytokinesis in mammalian cells, Kormophyten and baker’s yeast
- starts usually with the formation of an ingression furrow -> in somatic mammalian cells
- requires a break-down of the nuclear envelope - in somatic mammalian cells
- needs vesicle transport along microtubules to the mid-lane -> in somatic cells of a Kormophyte
- is always morphologically asymmetric -> in cells of Saccharomyces cerevisiae (Baker’s yeast) (in somatic mammalian cells)
- ends with a structure termed midbody -> Metazoa (Mammalian)
For the division of chloroplast the involvement of (2 I 3 / 4) different classes of GTPases are needed.
The inheritance of yeast vacuoles requires (a recruitment of ribosomes to the limiting membrane /a fragmentation of the vacuole / a complete block of the metabolic activity of the vacuole).
The fusion of somatic mammalian cells (can be observed in vivo / requires SNARE homologs as fusogenes / requires mitofusin homologs as fusogenes).
Contact sites between endoplasmic reticulum and mitochondria (are sites of lipid transport between ER and mitochondria / provide channels for the exchange of proteins between the ER lumen and the inter membrane space of mitochondria / define the sites of mitochondrial fission).
- 2
- a fragmentation of the vacuole
- can be observed in vivo
- define the sites of mitochondrial fission
The polyadenylation of a mRNA (is in the cytoplasm of eukaryotic cells always a stabilizing element / is in the nucleus in most cases a stabilising etement / is in the cytoplasm of prokaryotic cells a destabilizing element)
The identification of a so-called premature stop codon in mammalian cells (occurs in the nucleus / is only important for the cett in the case of selenium depletion / activates an mRNA-editing machinery to repair the defective codon).
Stress granules (are membranous organelles, which form in the cytoplasm / are sites for storage of ribosomes, mRNAs and preinitiation complexes / may exchange their materia! with so-called processing bodies).
The nascent chains of stalled ribosomes in cytoplasm yeast (are degraded via the proteasome / are covalently linked to the mRNA tagging the molecute for degradation / can be deposited in aggregates).
- is in the cytoplasm a prokaryotic cells a destabilizing element
- occurs in the nucleus? -> activates decay
- are sites for storage of ribosomes, mRNAs and preinitiation complexes
- are degraded via the proteasome
Link the statements (1 to 12) to the viruses (A and B) by writing the statement numbers behind the correct virus. Multiple links are possible (incorrect
answers cost points)
1. 2-,3- and S-fold symmetry
2. A hypodermic “nano”-syringe
3. Helicalsymmetry
4. 12 faces, each with a S-fold symmetry
5. 12 vertices, each with a S-fold symmetry 6. g8p major coat protein, 2700-3000 copies 7. =4
8. Amplitude and pitch
9. Jelly roll structures
10. P=µxp
1 1. Chymotrypsin-like fold 12. Canyon binder drugs
A. Phage M13: B. Picornaviruses:
PHAGE M13
- P = µ x p
- helical symmetry
- g8p major coat protein, 2700 - 3000 copies
PICORNAVIRUSES
- Jelly roll structures
a) The lnfluenza HA surface glycoprotein is a lectin.
b) HA auto-catalytically cleaves itself into two fragments, HAI and HA2.
c) The first 20 amino acids of the N-terminus of HA2 constitute the so-called fusoqenic peptide.
d) HA binds sialic acid residues of host-glycoproteins.
e) At high pH a substructure of HA rearranges into a 6-helix-bundle.
0 Fusion inhibitors affect HA 6-helix-bundle formation, which is mandatory for infectivity.
a) WRONG
b) WRONG
c) RIGHT
d) RIGHT
e) ?
f) RIGHT
Different statements regarding:
- Tat, transactivator of transcription
- lntegrase
- REV, regulator of expression of virion proteins
- Vif, viral infectivity factor
- Vpu, viral protein out Vpr, viral protein rapid
- Nef, non-evident function Proteinase
- Reverse transcriptase
- GP41
- GP1 20
- CA, capsid protein
- Vif- viral infectivity factor: Hijacks the cellular Cullin5 E3 ubiquitin ligase to ubiquitinylate APOBEC3G
- REV, regulator of expression of vision proteins: lnvolved in splicing and nuclear export of viralmRNA
- RNA-RNA duplex dependent RNase activity
- Tat, transactivator of transcription: Activates CDKg by binding to Cyclin T1 of elonqation factor P-TEFb
- Vpu, viral protein out: lnduces ubiquitinylation and deqradation of CD4
- CA, capsid protein: Penta- and hexamer tyPe Protomers
- Vpr, viral protein rapid: G2 cell cycle arrest to endorse viral LTR activity
- RNA-dependent RNA polymerase: Reverse transcriptase
- Nef, non evident function: MHC-class-1 and -2 antiqen reduction
Different statements regarding:
- Tat, transactivator of transcription
- lntegrase
- REV, regulator of expression of virion proteins
- Vif, viral infectivity factor
- Vpu, viral protein out Vpr, viral protein rapid
- Nef, non-evident function Proteinase
- Reverse transcriptase
- GP41
- GP1 20
- CA, capsid protein
- Vif- viral infectivity factor: Hijacks the cellular Cullin5 E3 ubiquitin ligase to ubiquitinylate APOBEC3G
- REV, regulator of expression of vision proteins: lnvolved in splicing and nuclear export of viralmRNA
- RNA-RNA duplex dependent RNase activity
- Tat, transactivator of transcription: Activates CDKg by binding to Cyclin T1 of elonqation factor P-TEFb
- Vpu, viral protein out: lnduces ubiquitinylation and deqradation of CD4
- CA, capsid protein: Penta- and hexamer tyPe Protomers
- Vpr, viral protein rapid: G2 cell cycle arrest to endorse viral LTR activity
- RNA-dependent RNA polymerase: Reverse transcriptase
- Nef, non evident function: MHC-class-1 and -2 antiqen reduction
Different statements regarding:
- Tat, transactivator of transcription
- lntegrase
- REV, regulator of expression of virion proteins
- Vif, viral infectivity factor
- Vpu, viral protein out Vpr, viral protein rapid
- Nef, non-evident function Proteinase
- Reverse transcriptase
- GP41
- GP1 20
- CA, capsid protein
- Vif- viral infectivity factor: Hijacks the cellular Cullin5 E3 ubiquitin ligase to ubiquitinylate APOBEC3G
- REV, regulator of expression of vision proteins: lnvolved in splicing and nuclear export of viralmRNA
- RNA-RNA duplex dependent RNase activity
- Tat, transactivator of transcription: Activates CDKg by binding to Cyclin T1 of elonqation factor P-TEFb
- Vpu, viral protein out: lnduces ubiquitinylation and deqradation of CD4
- CA, capsid protein: Penta- and hexamer tyPe Protomers
- Vpr, viral protein rapid: G2 cell cycle arrest to endorse viral LTR activity
- RNA-dependent RNA polymerase: Reverse transcriptase
- Nef, non evident function: MHC-class-1 and -2 antiqen reduction
Describe the pathway used by SV40 to its site of genome replication
- Endocytosis into Calveolae
- Fusion with Caveosome, no pH shift
- Long transport in vesicles; actin, Rho-GTPase and microtubule-dependent into the ER
- Structural rearrangement of the capsid in the reducing milieu of the ER, mysristylated N-term of VP2 exposed
- Penetration into cytoplasm; ERAD pathway! (ER-associated protein degradation complex)
- Import into nucleus by NPC and NLS in VP2/3
At which intracellular membrane system does the RNA replication of the
following viruses occur?
SARS coronavirus: ER
Sindhis virus (Alphavirus): modified Endosomes and lysosomes
Flockhouse virus: Outer Mitochondrial Membrane
Poliovirus: membrane-coated vesicles
Describe the properties of RIG I
-C-terminal regulatory domain
- 5’ PPP RNA (also when ss)
- short blunt ds region (also without 5’ PPP) e.g. panhandle of ss (-) RNA virus
- poly Uridine stretches
At which step does Influenza virus interfere with the RIG I signaling pathway? Which viral protein is required for interference
Influenza A virus nonstructural protein 1 (NS1) specifically inhibits TRIM25-mediated RIG-I CARD ubiquitination, thereby suppressing RIG-I signal transduction.
Virus evolution. What is a “bottle neck” experiment? Explain briefly by describing an example
- Selection: e.g. by neutralizing monoclonal antibodies or antivirals in cell culture supernatants
- massive reduction of heterogeneity in population
The infection of members of the genus Flavivirus involves the process of membrane fusion. What is the role of prM during maturation of the visions of these viruses? Describe this process and the role of prM.
prM: protection form fusion during budding; Turin cleaves prM into pr and M (in TGN)
1) Co translational association with helper protein (e.g. prM in Flavi-, E2 for Alphaviruses)
2) Helper protein blocks fusion activity; protects virus from premature fusion
3) proteolytic cleavage of helper proteins is a requirement for fusion activity of the fusion protein
4) Due to a low pH in the secretory pathway, pr peptide remains bound to E even after proteolysis and still protects virus from premature fusion with the host cell membrane
5) After secretion into the extracellular milieu (neutral pH), pr peptide is released and the fusion loop in E (internal loop not terminal like class I fusion peptide) becomes fusion active
6) At neutral pH E is a dimer lying flat on the vision; at low pH in the end-some E is converted into a conformation protruding from the vision surface which allows insertion of the fusion loop onto the Endosomal membrane
7) this triggers trimerisation of E which triggers the conformational change leading to the approach of membranes and their fusion
How are retroviruses traveling directly from cell to cell? Describe briefly the mechanism and the functional role of the cell associated retroviral ENV protein in this process?
ENV: promotes export of mRNA out of the nucleus
spread cell-to-cell by induction of multimolecular complexes termed virological synapses that assemble at the interface between infected and receptor-expressing target cells.
Describe the domain structure of the protein “p” of Hepatitis B virus in a scheme.
- inckudes motifs in Pol/RT and RH which are shared with retroviral RT
Additional domain: TP (terminal protein)-domain without know homolog
Before “p” can start the cDNA synthesis on the viral RNA an activation step is required. Describe this activation step and explain the priming reaction in detail. Name the involved molecules and explain the individual steps with a scheme.
All DNA-polymerases need a “primer” (3’-OH end) for initiation of DNA synthesis
- 5’ base of (-)-DNA covalently bound to tyrosine in TP-domain of P > “protein priming”
- P protein accepts no other template RNA than pgRNA (<>cDNA synthesis!=
- 5’ end of (-)-DNA localizes in 3’ proximal DR1 (direct repeat 1)
- UUC sequence in DR1 exists also in the epsilon bulge region (sequence of duck HBV)
- Its complementary sequence AAG in the (-)-DNA represents a copy thereof
- epsilon contains origin of replication for (-) DNA
- (-) DNA Synthesis is discontinuous
-> Retroviruses are similar in their mechanisms
The cellular m:R-l22 is a critical host factor for the Hepatitis C Virus life <ycle. Which of the statements Goncerning the mechanisti< and/or functional features for miR-I22’s role in the HCV life cycle given below are correct?
- miR-122 stimulates HCV RNA synthesis prior to promoting viral protein synthesis by displacing PCBP2 from the viral RNA genome via competition with PCBP2 for binding to the 5’ UTR. This mode of action promotes an open, noncircular genome conformation
Proteins using the GEP (general excretion pathway) may be translocated (while being synthesized (cotranslationally) / after termination of their synthesis / before termination of transcription of the corresponding gene).
- while being synthesized (cotransaltionally)
The GEP is the only pathway that (transports soluble proteins into the periplasm / that integrates membrane proteins into the plasma membrane / that integrates porins into the plasma membrane).
- that integrates membrane proteins into the plasma membrane
In some pathways, the GEP-dependent transport is regulated by (a GTPase / a system of two GTPases / is only regulates by ATPases).
- is only regulated by ATPases
The GEP is usually able to transport (unfolded proteins / folded proteins / tRNAs).
- folded proteins
The periplasmic space of E. coli (is reducing and thus allows the formation of disulfide bridges / is ATP-rich and thus allows the folding of proteins / is free of soluble proteases, therefore misfolded soluble proteins need to be reimported into the cytoplasm for degradation).
- is free of soluble proteases, therefore misfiled soluble proteins need to be reimported into the cytoplasm for degradation
For the maintenance of the outer membrane of E. coli (proteins with ß-barrel folds must be integrated / lipopolysaccharides must be translocated to the outer leaflet / cholesterol is translocated across the periplasm).
- lipopolysaccharides must be translocated to the outer leaflet
The translocation of nuclear-coded proteins into the matrix of mitochondria occurs with the direct involvement of (the TOM-complex / the TIM22-complex / mtHSP70).
- the TOM-complex
- the TIM22-complex
TIM 9/10 is a complex of the intermembrane space, which is essential for the (integration of carrier proteins into the inner membrane / the translocation of proteins into the matrix / the biogenesis of ß-barrel proteins of the outer membrane) whos activity depends on the presence of (ATP / GTP / CTP).
- Integration of carrier proteins into the inner membrane?
- ATP
Proteins of the matrix that do not fold properly are usually degraded (in the matrix / in the intermembrane space / in the cytoplasm).
- in the cytoplasm
Name the two ways discussed for the formation of Secretory granules (dense core vesicles).
- Condensing vacuole model
- homotypic fusion model
Describe the major differences between „fluid-phase endocytosis“ and “receptor-mediated endocytosis“. Would the term „Pinocytosis“ match to any of these processes, and if so, why?
- low efficiency, non specific
- nonspecific mammalian cells drink about one volume per day
- nutrients may be concentrated in lysosomes by uncharacterized mechanisms
-> can be summarized as Pinocytosis “senso stricto”
Receptor mediated endocytosis: uptake of up to 30 % of bound ligands per minute
„Multivesicular bodies“ (MVB) can be part (of a degradation pathway / of a secretion pathway). They contain internal vesicles, into which (membrane proteins / soluble proteins) are sorted, which usually have been tagged before by a
(monoubiquitination / sumoylation / polyubiquitination).
- of a secretion pathway
- membrane proteins
- ?
The following parts of a cell can be selectively targeted by autophagy (peroxisomes / mitochondrial ribosomes / midbodies). During formation of the autophagosome in macroautophagy lipids in the phagophore are (modified via O-glycosylation / modified via ubiquitination / enriched in sphingomyelin). In chaperone-mediated autophagy (only small organelles are digested / chaperones located in the lysosomal lumen are involved / cytoplasmic ATPases are involved).
- peroxisomes, ribosomes,
- modified via ubiquitination
- chaperones located in the lysosomal lumen are involved
Name three fundamental mechanisms that are responsible for the asymmetric distribution of lipids between the leaflets of the plasma membrane
Most of the Phosphatidylserine (PS) is located on the cytosolic site of the plasma membrane
- Generation and maintenance of PS asymmetry by an energy-dependent flip-awe (ATP hydrolysis)
Which are the two main pathways for delivery of lipids from the ER to the TGN?
early targeting at Lipid droplet formation sites during formation, and late targeting to mature lipid droplets after their formation
During cytokinesis the new plasmamembanes are formed (before disassembling of the actin ring / under involvement of ESCRT-proteins / after division of the midbody into two equal pieces) The source of the additional membrane needed is mainly from (the outer mitochondria membrane | the peroxisome | the outer shell of lipid droplets). During open mitosis, the disassembling of the nuclear membrane requires (the phosphorylation of proteins of the nuclear lamina / the proteolysis of the nuclear pore / the transformation of sheet-like ER into tubular ER). ER-stacks in professional secretory cells like B-cells are only stable in the presence of (tight junctions / neurofilaments / ER-cisGolgi contact sites).
- after division of the middy into two equal pieces
- by fusion of vesicles
- the transformation of sheet-like ER into tubular ER
- ER-cis Golgi contact sites
Which function have sno / scaRNA during ribosome biogenesis? Where in the cell do they perform this function precisely? Are members of these RNAs also involved in the biogenesis of other RNPs and if so of which ones?
- guide modification in the nucleoli
-> Box C/D snoRNAs guide 2’O methylation
-> Box H/ACA snoRNAs guide pseudouridylation
Capsid of human rhino virus
- Canyon-binder drugs target VP1 and prevent uncoating of the viral capsid.
- 5 copies of VP1 form the so-called “molecular mountains”.
Bacteriophage MS2
- The capsid triangulation number T equals 3 (T=3).
- The icosahedron shell is made up of a single type of coat protomer.
Influenza virus Neuranimidase (NA)
- HA is cleaved by the host cell tryptase Clara into two fragments, HA1 and HA2
- ## The so-called fusogenic peptide, exposed at low/acidic pH, is part of the HA2 fragment.
Link the statements (1 to 12) to the proteins (A to D) by writing the statement numbers behind the proteins/colons. Multiple links are possible.
(incorrect links lead to the deduction of points)
1. CCR5
2. RNA polymerase II
3. Proofreading
4. Ubiquitin ligase recruitment to degrade cellular cytidine deaminase
5. Crm1 - Ran.GTP - eIF-5A export pathway
6. Arrest of proliferating cells at G2/M phase
7. CD4 receptor binding to evoke receptor ubiquitination and degradation
8. 6-Helix-bundle formation
9. tRNA(Lys3)
10. Regulator of viral RNA splicing
11. RNAseH Domain
12. Affects the innate defense factor APOBEC3G
A GP120
B Reverse Transcriptase
C Vif protein
D Rev protein
- Vif protein: ubiquitin ligase recruitment to degrade cellular cytidine deaminase
- Reverse Transcriptase: tRNA (Lys3), RNAseH Domain
- Vif protein: Affects the innate defense factor APOBEC3G
At which membrane does the budding of retroviruses occur?
- ER membrane
- intermediate compartment
- Golgi membrane
- plasma membrane
- plasma membrane
Which cellular pathway and protein complexes are involved in retroviral budding? State the names of the pathway and protein complexes.
D type retrovirus preassembled “Gag” particles
Which signals in the viral proteins are recognized by the cellular proteins in this pathway?
State the name of the signal and describe it in detail for one viral protein and name for this viral protein its cellular interaction partner.
HA and M2 are required for budding and release
- amphipathic helix of M” is sufficient to induce vesicle budding and release
- localizes to the point of membrane scission (neck) (immmuno-gold labeling)
- virus mutant in M2 helix is impaired in membrane scission
-> virus arrays: like beads on a string
- M2 is essential for pinch off
(+)-strand RNA viruses restructure the intracellular membrane systems of the host cell for their genome replication.
Name for each of the compartments listed below one virus which makes use of these membranes for genome replication:
- ER
- Golgi
- Lysosomen
- Mitochondrien
ER: Kunjin virus (Flavivirus)
Golgi: Kunjin virus (Flavivirus)
Lysosomen: Rubella virus
Mitochondrien: Flock house virus
For viruses restructuring the ER two basic models/mechanisms how the membrane spherules are generated were postulated based on these analyses. Name the two models/mechanisms and give for each one a viral example.
- Virus induced membrane vesicle
- replicating RNA reistant to RNAses
- NTPs etc must have access
- shielding from immune system? (“innate immunity”; interferon)
Describe a technical device (apparatus) which allows to study the polarity of virus release from infected cells? Use a scheme.
Explain why a certain cell type is required for such a study. Name cell type and its specific features.
State one viral example (virus and family) for each of the possible polarities.
Cell culture in a membrane coated chamber; selective release of viruses into the media above or under the cells?
Epithelial cells which can be divided into apical (towards the environment) and basolateral (towards the inside of the body)
Apical: Paramyxoviridae -> SARS coronavirus
Basolateral: Crimean-Congo hemorrhagic fever virus
Explain the generation, the function/mode of action of the pr peptide during virion morphogenesis for members of the genus Flavivirus.
- Due to a low pH in the secretory pathway, pr peptide remains bound to E even after proteolysis and still protects virus from premature fusion with the host cell membrane
- after secretion into the extracellular milieu (neutral pH), pr peptide is released and the fusion loop in E (internal loop not terminal like class I fusion peptide) becomes fusion active
A minority of viruses utilize non-canonical mechanisms in the biogenesis of miRNA molecules. Which of the following answers is/are correct/wrong?
- some viral pre-miRNAs are transcribed by RNA polymerase III
- all viral pre-miRNAs are exported into the cytoplasm by exportin-5
- all viral pre-miRNAs are processed by dicer
Der SecY-abhängige post-translationale Transport von Proteinen über den General Excretion Pathway (GEP) verwendet als Energiequelle [ ATP | die PMF | GTP ].
- ATP
Der GEP ist beteiligt an der [ Sekretion von Proteinen mittels Autotransportern | beim TAT-Transportweg | bei der Biogenese von Typ I Pili ].
- beim Tat-Transportweg
Typ III Sekretion benutzt einen makromolekularen Komplex [ der drei Membranen durchqueren kann | der homolog zu Teilen bakterieller Flagellen ist | der ausschließlich co-translational funktioniert ] .
- der drei Membranen durchqueren kann
Die Typ I Sekretion verwendet als ATPasen Vertreter der [ ABC-Transporter | der AAA-ATPasen | der F0/F1-ATPasen ] .
- ABC Transporter
Der Import von Proteinen in die Matrix der Mitochondrien verwendet eine [ saure | amphipathische | hydrophobe ] Signalstruktur, die in Gegenwart ihres Rezeptors
[ eine Helix | eine ß-Faltblattstruktur | ein sogenanntes ß-barrel ] bildet.
- ## hydrophob
Das Mitochondriengenom der Säuger codiert für [ Proteine der äußeren Mitochondrienmembran | Proteine der inneren Mitochondrienmembran | tRNAs der Matrix ] .
- tRNAs der Matrix
Im Zellkern codierte Säugerproteine der inneren Membran, die ein internes Targetingsignal besitzen, nutzen zur Insertion [ den TOM complex | den TIM 22 complex | das mtSecY ] .
- den TIM22 complex
Ordnen Sie die nachfolgend genannten Komponenten des Proteintransportes in die Chloroplasten dem Kompartiment zu, in dem sie vorkommen. Geben Sie auch an, in welchem Kompartiment die Abspaltung des Transitpeptides erfolgt.
Komponenten: TOC, TIC, cpSecY, cpTAT
Äußere Membran
Intermembranraum
Innere Membran
Stroma
Thylakoidmembran
Das Transitpeptid wird im …………………… abgespalten.
Äußere Membran: TOC
Innere Membran: TIC
Thylakoidmembran; cpSecY
Stroma: cpTAT
Das Transitpeptid wird im Strom gespalten.
Welche(r) der genannten Mechanismen kommt beim „dual targeting“ tatsächlich vor?
[ Ein Molekül einer Population gelangt zu einem Zeitpunkt X entweder in ein Kompartiment A oder in ein Kompartiment B. | Jedes Molekül der Population kommt zumindest teilweise in Kontakt zu Kompartiment A, bevor es entweder in A verbleibt oder nach B umdirigiert wird. | Moleküle gelangen in Abhängigkeit von zellphysiologischen Zuständen eher nach A oder eher nach B ].
Moleküle gelangen in Abhängigkeit von zellphysiologischen Zuständen eher nach A oder eher nach B ].
Der COPII-coat ist am Transport vom ………….. zum ……………. beteiligt.
Der KDEL-Rezeptor dient der Rückführung von Proteinen aus dem ……………………… zum ……………. .
Der Import von Zuckern in den Golgi erfolgt mittels [ Isoprenen über Flippasen | Antiportern | Hexose resp. Pentose-Phosphaten als Transportform ].
In Säugerzellen befinden sich die ER-exit sites [ i.d.R. in der Nähe des Golgi- Apparates | über das ER-Netzwerk verteilt | auch an der inneren Kernmembran].
Ein entscheidender Auslöser für die Aktivierung von Preproteinkonvertasen
ist der im Verlauf des sekretorischen Weges …………………… pH-Wert im Lumen.
Der COPII coat ist am Transport vom ER zum ERGIC/cis-Golgi beteiligt.
Der KDEL-Rezeptor dient der Rückführung von Proteinen aus dem Cis-Golgi zum ER.
- antiportern
- i.d.R. in der Nähe des Golgi-Apparates
Ein entscheidender Auslöser für die Aktivierung von Preproteinkonvertasen ist der im Verlauf des sekretorischen Weges SAURE pH-Wert im Lumen.
Synaptische Vesikel der Säuger haben normalerweise einen Durchmesser von [ 2nm | 2 μm | 2mm ] .
Die Fusion der Vesikel wird durch den Einstrom von ……………-Ionen getriggert.
Tetanusneurotoxin hemmt die Fusion synaptischer Vesikel ……………………………………….. eines SNARE –Proteins.
Die Endocytose von Rezeptoren kann [ mittels Clathrine-coats | mittels Caveoline| mittelsCoatamer]erfolgen.
- 2 nm
- Calcium-Ionen
- SPALTUNG eines SNARE-Proteins
- mittels Clathrine-coats
Der spezifische Abbau von Lipidvesikeln in Lysosomen wird ermöglicht durch die schützende Wirkung der ……………………………….. auf die Grenzmembran der Lysosomen und die destabilisierende Wirkung von …………………………………………… auf die internalisierten Membranvesikel.
- Aktivatoren
- Special lipid composition and a low lateral pressure
Beschreiben Sie in drei Hauptphasen der Zytokinese bei Säugerzellen
- Anaphase - Telophase
- begin go the assembling of the constriction ring at the PM in the midplane of the cell
- ingression of the furrow by the actin-myosin ring till the spindle in the midplane is compressed -> formation of midbody - Abscission
- disassembling of the contractile ring and the spindle in parallel to the sealing of the PM
Kreuzen Sie die richtigen Aussagen an.
Im Rahmen der „organellar inheritance“ während der Mitose fusionieren große Teile des Golgi-Apparates mit dem endosomal/lysosomalen Kompartiment.
Bei der Teilung der Chloroplasten wird zuerst das Membransystem der Thylakoide, dann die innere Membran und zum Schluss die äußere Membran geteilt.
Die homotypische Fusion von Mitochondrien der Säugerzellen erfolgt mittels SNARE-Proteinen.
- Im Rahmen der „organellar inheritance“ während der Mitose fusionieren große Teile des Golgi-Apparates mit dem endosomal/lysosomalen Kompartiment.
- Bei der Teilung der Chloroplasten wird zuerst das Membransystem der Thylakoide, dann die innere Membran und zum Schluss die äußere Membran geteilt.
Neben rRNA, tRNA und mRNA haben eukaryontische Zellen verschiedene evolutionär konservierte sogenannte „kleine RNAs“.
Nennen Sie drei Beispiele hochkonservierter Arten und ihre Funktion in der Zelle
-> miRNA: may regulate the function and stability of target mRNAs by different mechanisms
-> piRNA: down regulation of transcripts form transposons thus controlling their spreading in the genome
-> endogenous siRNA: can repress gene expression post transcriptionally but have also been shown to affect transcription of specific loci and chromosome structure
Die Insertion von Proteinen in die innere Membran von E. coli erfolgt
(immer / in der Regel / selten) post translational. Als wichtige Membranproteine
können daran (SecYEG / YidC / TRAP) beteiligt sein.
- immer
- SecYEG / YidC
Der TAT-pathway (kann mit Cofaktoren beladene, gefaltete Enzyme über die innere Membran transportieren / verwendet oft lepB zur Abspaltung des Targetingsignales / wird durch Argenine im N-terminalen Bereich des Targetingsignales blockiert).
- kann mit Cofaktoren beladene, gefaltete Enzyme über die innere Membran transportieren / verwendet oft lepB zur Abspaltung des Targetigsignales
Proteine der äußeren Membran von Proteobakterien (sind in der Regel mittels alphahelikalen hydrophoben Abschnitten in der Membran integriert / werden oft vermittels des SecYEG-Komplexes über die innere Membran transportiert / sind – genauso wie die LPS-Moleküle der Membran – immer stark glycosyliert).
- werden oft vermittels des SecYEG-Komplexes über die innere Membran transportiert
Proteine der äußeren Membran von Proteobakterien (sind in der Regel mittels alphahelikalen hydrophoben Abschnitten in der Membran integriert / werden oft vermittels des SecYEG-Komplexes über die innere Membran transportiert / sind – genauso wie die LPS-Moleküle der Membran – immer stark glycosyliert).
- werden oft vermittels des SecYEG-Komplexes über die innere Membran transportiert
Describe the properties of RIG I
- retinoid acid inducible gene I
- Helikase -> intracellular receptor
- restriction factor
- recognizes RNA viruses like Hepatitis C, Influenza
- pattern recognition receptor
Which of the following statements about the capsid of tomato bushy stunt virus is/are wrong? Multiple answers are possible.
(incorrect answers lead to the deduction of points) (2.5 P)
a) The capsid protein has 3 domains (R, S and P) and can adapt to 3 different environments.
b) The capsid triangulation number T equals 3 (T=3).
c) The P-domains form in total 60 protrusions on the outer surface of the capsid.
d) The icosahedron shell displays 12 x 5-fold, 20 x 3-fold and 30 x 2-fold rotation axis.
e) The small S domains cover the outside of the capsid and form an external framework.
Wrong answers are:
c) The P-domains Form in total 60 protrusions on the outer surface of the capsid.
d) The icosahedron shell displays 12 x 5-fold, 20 x 3-fold and 30x2-fold rotation
e) The small S domains cover the outside of the capsid and form an external framework.
Which of the following statements about the capsid of picornaviruses is/are wrong? Multiple answers are possible.
(incorrect answers lead to the deduction of points)
a) The capsid contains 60 copies each of proteins VP1 to VP4.
b) VP2 and VP3 are located at the top of the so-called molecular mountains. c) VP1 to VP3 form jelly-roll-barrel structures.
d) The capsid triangulation number T of picornaviruses equals 4 (T=4).
e) Canyon-binder drugs target VP1 and prevent uncoating of the viral capsid. Wrong answers are:
b) VP2 and VP3 are located at the top of the so-called molecular mountains.
d) The capsid triangulation number T of picornaviruses equals 4 (T=4).
Which statements concerning potential modes of action of viral miRNAs are correct?
(cross correct answers; wrong answers will lead to the deduction of points)
(2.5 P)
Viral miRNAs can regulate the translation of viral transcripts if the miRNAs are not 100 percent complementary to the viral target mRNAs.
miRNAs of DNA viruses can stimulate the RISC-mediated destruction of viral transcripts if the miRNAs have been transcribed in „antisense“ orientation to the corresponding viral transcript.
miRNAs of DNA viruses can stimulate the RISC-mediated destruction of viral transcripts if the miRNAs have been transcribed in „sense“ orientation to the corresponding viral transcript.
Viral miRNAs can function as orthologs of cellular miRNAs if they share with these cellular miRNAs an identical 6 nucleotides long sequence at the 5‘-end of the miRNA.
Viral miRNAs can function as orthologs of cellular miRNAs if they share with these cellular miRNAs an identical 6 nucleotides long sequence at the 3‘-end of the miRNA.
- Viral mRNAs can regulate the translation of viral transcripts if the miRNAs are not 100 percent complementary to the viral target mRNAs
- miRNAs of DNA viruses can stimulate the RISC-mdeiated destruction of viral transcripts if the miRNAs have been transcribed in “antisense” orientation to the corresponding viral transcript.
Viruses use different routes for infection. Name for each route one viral example and state whether the virus replicates there or spreads systemically:
(wrong answers will lead to the deduction of points)
Digestive tract:
Eye:
Urogential system:
Digestive tract:
Local replication -> Corona
Eye:
Local replication: Adenovirus
Urogenital system:
Local replication: HPV
Viruses have different tissue tropisms. Name one example for each of the following tropisms.
(wrong answers will lead to the deduction of points)
Epithelotropic:
Lymphotropic:
Neurotropic:
Hepatotropic:
Epithelotropic: Papilloma Virus
Lymphotropic: Eppstein Barr Virus
Neurotropic: Herpes virus
Hepatotropic: Hepatitis Pathogenese HAV, HBV, HCV
Name four mechanisms how to bend a membrane
CLUSTERING
Transmmebrane proteins with inherent curvature inducing curvature in a membrane
MOTIF INSERTION
Insertion of a piece of a protein into one leaflet of the membrane induces curvature
BAR DOMAINS
A BAR domain of a protein inducing and stabilizing the curvature of a membrane
SCAFFOLDING
- cage like structure of Cathrin
- when this structure forms around a membrane, it pulls the membrane into a tight curvature until eventual vesicle budding
CYTOSKELETON
The inherent shape of a cell as controlled by its cytoskeleton requires that the bilayer membrane curves around it
Name four viruses from different families (name virus and family) which can cause hemorrhagic fever
- Flavivirus: Dengue, Yellow Fever
- Bunyaviruses: Crimean-Congo hemorrhagic fever virus (CCHFV)
- Hantavirus
Which ARBO virus was recently introduced into the Americas and is suspected to cause severe brain damage in human fetuses? Name virus, family, genus and
vector.
Zika Virus
Familie: Flaviviridae
Genus: Flavivirus
List three cellular sensors of double stranded RNA
- RIG I like receptors
- protein kinase R
- oligoadenylate synthases
- adenosine deaminase
What other features of an RNA can be recognized by the innate immune system? Name the features and the relevant sensors for the innate response.
PPPRs = pattern recognition receptors
PAMP = pathogen associated molecular pattern
How does Influenza virus interfere with signal transduction upstream of IPS1 (=MAVS, CARDIF, VISA)?
Influenza A virus nonstructural protein 1 (NS1) specifically inhibits TRIM25-mediated RIG-I CARD ubiquitinazion, thereby suppressing RIG-I signal transduction.
What was the so called “Rabbitpox-Experiment”? What was the outcome and what could be learned?
Release of Myxomatosis-virus to control population of European rabbit introduced by immigrants
-> Spread by fleas and mosquitos (passive, no replication in Athropodes)
-> 90 - 99 % lethal for European rabbits
- year: Mortality rate 99,8 %
-> Effizienz killing of rabbits - year: Mortality rate only 25 %
-> Rapid selection of adaptive mutations in the virus (and the host)
-> Attenuated virus variants / host population in between only a few years
Later years
-> Mortality lower than birth rate of rabbits
ADAPTION BETWEEN HOST AND VIRUS!
(kind of “bottle neck experiment” -> the ones that couldn’t cope died)
Which of the following statements about the Influenza virus Neuranimidase (NA) and Hemagglutinin (HA) is/are wrong? Multiple answers are possible.
(incorrect answers lead to the deduction of points)
HA is cleaved by a host cell tryptase (Clara) into two fragments, HA1 and HA2.
The so-called fusogenic peptide, exposed at high pH, is part of the HA1 fragment.
NA is a muraminidase that can be inhibited by Penicillin.
4 NA molecules, each displaying a 4-bladed propeller, form the functional biological unit.
Fusion Inhibitors affect HA 6-helix-bundle formation required for infectivity
- HA is cleaved by a host cell try-taste (Clara) into two fragments, HA1 and HA2.
- The so-called fusogenic peptide, exposed at high pH, is part of the HA1 fragment.
- NA is a muraminidase that can be inhibited by Penicillin.
Link the items (1 to 10) to the viruses (a to c) by writing the item numbers behind the viruses (behind the colons). Multiple links are possible.
(incorrect links lead to the deduction of points)
1. Triangulation number T = 3
2. ±16 (16.3) coat proteins per helical turn
3. Jelly roll of 8 ß-strands and a Greek key motif
4. Non-enveloped DNA virus
5. Viral lysozyme required to enter the host cell
6. 3 copies each of VP1 and VP4 arrange around pseudo 6-fold rotation axes
7. 60 copies of VP1 to VP4
8. Total of 12 x 5-fold, 20 x 3-fold and 30 x 2-fold axes
9. Canyon binder drugs
10. A few thousand coat protein copies make up the capsid
a) Tobacco mosaic virus:
b) Picornavirus:
c) Bacteriophage T4:
a) Tobacco mosaic virus:
- 16.3 coat proteins per helical turn
b) Picornavirus:
- 60 copies of VP1 to VP4
- Triangulation number T = 3
- Canyon binder drugs
c) Bacteriophage T4:
- Triangulation number T = 3
Name three viruses with high tissue specificity and three with low tissue specificity:
(wrong answers will lead to the deduction of points)
High tissue specificity:
Low tissue specificity:
High tissue specificity:
- Herpesviruses
- Papillomaviruses
- Retroviruses
- Hepatitis Viruses
Low tissue specificity:
- Alphaviruses
- Genus Flavivirus
- Rabies virus
Some humans have a genotype which protects them against infection by certain viruses. Name two human gene variations and the viruses against which they are protective as well as the putative underlying mechanisms.
HCV
- Genetic variation in IL28B
-> upstream region of IL28B gene = IFN gamma 3 = IFN class 3 molecule
SARS-CoV
- Trim 55
