Revision Flashcards
What happens when a signal sequence binds to the translocator?
The plug which normally blocks the pore is removed
Where do disulphide bonds occur?
- Between cysteine amino acids
- Doesn’t occur in the cytoplasm as the cytosol reduces cysteine residues
What is ubiquitin?
A 76 -78 residue protein
What are adherens junctions controlled by?
Ca2+
How does ubiquitylation occur?
1) Degredation signal recognised by E3 (ubiquitin ligase)
2) E3 is associated with E2 (ubiquitin- conjugating enzymes)
3) E2 has ubiquitn attached
4) Brought into close contact with target protein - can ubiquinate the protein
What is the smooth ER responsible for?
Synthesis of:
- Phospholipid
- Cholesterol
Synthesis and storage of:
- Glyserides
- Glycogen
Storage of:
- Ca2+
Production of:
- Steroid hormones`
Describe transitional epithelium
- Stratisfied
- Can switch between squamous (bladder full) and columnar (bladder empty)
What is depurination?
- A or G lost from the DNA backbone
- Replaced with random base if not repaired
What are heat shock proteins?
- Molecular chaperones
- Create the right environment for proteins to correct missfolding (have hydrophobic surfaces)
- Synthesised more at high temperatures where there is more chance of missfolding
- Use ATP hydrolysis
What is deamination?
- C change to U
- If not repaired, U pairs with A
- GC –> TA
How are gap junctions regulated?
- Membrane potential
- pH
- Ca2+
- Neurotransmitters
Prevents damage by Ca2+ influx
Which proteins must be moved cotranslationally and what must they have in their DNA sequence?
- ER membrane
- Golgi membrane
- Plasma membrane
- Secretory
- Lysosomal
Must have a sorting sequence which mediated attachment to the ER membrane
What causes receptors to release their cargo inside the cell during receptor-mediated endocytosis?
Low pH of the endosome
What is the process of triggered phagocytosis?
1) Optenisation of pathogen (antibodies cover the surface)
2) Antibodies bind to Fc receptors on phagocyte
3) Extension of pseudopods by mobilistion of actin
4) Zippering mechanism
5) Form phagosome
What is dynamin?
- GTPase
- Required for clathrin mediated uptake to form the pit
- GTP hydrolysis is what causes the vesicles to bud off from the membrane
What makes tight junctions different from each other?
Different types of claudin expressed in different combinations
- 24 different types of claudin
What is pinocytosis?
- Cell ‘drinking’
- Membrane invaginates and pinches off to form a vesicle
How are proteins marked for destruction?
Covalent attachment of poly-ubiquitin at lysine 48
Example of a base modifier and what do they do?
- Alkylating agents (EMS, EMU)
- Adds akyl groups to bases
eg. forms methylguanine, which is an analogue of adenine
- Pairs with thymine
What is a signal recognition particle and how does it work?
- Binds to a signal sequence on a protein as it comes out of the ribosome
- Hinge bends around the ribosome complex and pauses translation
- Directs the complex to a specific receptor on the RER membrane (SRP binds to the receptor)
- Translation no longer paused
- Signal sequence in close contact with translocator - can bind and the protein can move into the RER lumen
What is the structure of gap junctions?
- 6 connexins make 1 connexon
- 1 connexon in each membrane forms gap junction
- Connexins are 4-pass transmembrane protein
Proteins in adhesion junctions?
Integrin (transmemebrane)
Adaptor proteins:
- Vinculin
Talin of filamin
What do intercalating agents do and what is an example?
- Insert bases into DNA
- Ethidium bromide
What is a neomorph mutation?
Gain-of-function
What does UV radiation do to DNA?
Form thymine dimers
What are the adaptor proteins in desmosomes?
- Contained within the cytoplpasmic plaque
- Desmoplakin, plakoglobin
What do focal adhesion junctions do?
Connect actin in the cytoskeleton to the extracellular matrix
Where is stratisfied epithelium found?
In areas with constant abrasion
What are the 4 fates of endocytosed material?
1) Degredation in the lyosome
2) Storage
3) Transcytosis - uptake at one membrane and released from another
4) Recycling - released back at the same membrane
What is the difference between the cadherins in adherens junctions and in desomosomes?
In adherens they are classical
- Have cadherin in their name
In desmosomes they are non-classsical
- Desomoglein
- Desmocolin
What is the stop sequence for a protein moving through the translocator?
Hydrophobic amino acids which bind to the translocator
What mutation occurs in ras and what does this cause?
- Missense mutation of amino acids whose side chains are critical for GTPase reaction
- Allows the alpha subunit to remain in the GTP-bound confimation
- Active
How is the cycling of ras (a GTPase) regulated?
In the golgi:
- Farnesylated and palmitoylated
- Allows trafficing via vesicles to the PM
At the plasma membrane:
- Ras is active
- Depalmitoylated to regulate, back to endomembranes
What is the structure of the proteasome?
- 2 caps and an active zone
Cap:
- Has a receptor which binds to ubiquitin
- Has ubiquitin hydrolase
- Ring of ATPases which through ATP hydrolysis unfolds the protein as it moves through
- Broken down by proteases which line the core
What is pemphigus?
Autoimmune disease
- Desomglein recognised as foreign and attacked by the immune system
What are the 4 functions of the rough ER?
1) Synthesis of secretory protiens and lipids
2) Storage of Ca2+ and glygogen
3) Transport of proteins
4) Detoxification of alchol
What is a tertiary protein?
Packing of secondary structures into proteins or subdomains (individual functional units of a protein which can fold and function independently)
What are the 3 functions of the golgi?
1) Modification and packing of secretions
2) Renewal and modification of the plasma membrane
3) Delivery of material to other organelles
What does signal peptidase do?
Cleaves the signal sequence on a protein in the translocator
What are the two types of cadherin in adherens junctions and why are they important?
N- cadherin (contract)
E- cadherin (don’t contract)
- Allows the formation of tubes in morpogenesis due to selected invagination
- Attach actin and myosin to the adhesion belt
What catalyses peptide bond formation?
Peptidyl transferase
What is prenylation?
Lipid anchors
Farnesyl
- Thioester linkage
- Cysteine
Geranylgerynyl
What is ploidy?
Difference in chromosome number
Where is connective tissue derived from?
Mesoderm
What does receptor-mediated endocytosis allow?
- The uptake of molecules with low abundance
- Selective
- Little undesired uptake
What transport occurs from the cytosol to the nucleus?
Gated transport
Example of a base analogue and what do they do?
- 5- bromouricil
- Pairs with guanine
What makes up the basment membrane?
Basal lamina and reticular lamina
What mutation causes anemia?
- Missense mutation of Hb-A gene
- Glutamic acid (charged) to valine (neutral)
What do zonulae occluden proteins do?
- Bind claudin or occludin to the cytoskeleton
- They are adaptor proteins
What does the abnormal prion protein do?
Recruits normal prion protein and induces it to change shape and form an aggregate
- Resists protease action
- Has the same sequences as the normal protein but different confirmation
What is clatherin made of?
- Triskelia
- Has 3 heavy and 3 light chains
- Make a lattice, cage-like structure
What are the proteins in tight junctions?
Claudins
Occludins
What is the adaptor protein in adherens junctions?
Catenin
Which glands secrete proteins?
Serous glands
- Have flat nuclei
What is connective tissue involved in?
- Storage
- Repair
- Transport
- Protection
What is acylation?
Lipid anchors
Myristyl
- Amide linkage
- Irreverible
Palmitoyl
- Thioester likage
- Cysteine
How does the ER resolve missfolding in its lumen?
1) It has its own chaperones
2) Has disulphide isomerase which breaks H bonds and allows other bonds to form
3) Taken out of translocator protein if missfolded which has ubiquitin ligase attached - attaches ubiquitin as leaving
Golgi cisternea?
- Cis golgi network (where vesicles are recieved from the ER)
- Cis cisterna
- Medial cisterna
- Trans cisterna
- Trans golgi network (where vesicles are released)
Where does ALL endocytosed material go to?
- The early endosome
- If included in the late endosome it is designated for destruction
What are translocators specific to?
The type of signal sequence, not the exact sequence
What does ubiquitination cause?
Mono
- Histone regualtion
Poly - DNA repair or - Proteasomal degredation (depending upon the site)
Multi
- Endocytosis
What are nuclear import receptors?
- Recognise nuclear localisation sequences and transport proteins through the nuclear pore complex
Where do protein modifications occur?
On reactive protein side chains
Are epithelia innovated and avascular?
Avascular (no blood vessels)
Not innovated
How does Ran work in the nucleus?
- Is a GTPase
- Ran/GTP in nucleus
- Binds to importin and causes it to release its cargo
- Ran/GTP carries the importin into the cytosol
- Ran/GTP –> Ran/GTP releases the importin
- Ran/GDP binds to importin with cargo and moves it through the nuclear pore
- Ran/GDP –> Ran/GTP
What are the resident proteins of the ER and what is their retension sequence?
PDI and BiP
4 amino acids at the C terminus
Describe pseudo-stratisfied epithelium
- Looks like several layers of nuclei
- But actually all cells lie on the basement membrane
- Some cells are just taller and some are shorter
How is syap-25 regulated?
Palmioylation patterns regulate membrane associated with specific membranes
When do amyloid fibrils become pathogenic?
- When they become stable and tightly bound
- Don’t dissociate
- Become aggregates causing cell death or accumulation
What are the 3 types of vesicle coat and when are they used?
COP II - bud off from ER
COP I - bud off from golig cisterna
Clathrin - Bud off from trans gogli network
What is phagocytosis?
- Cell ‘eating’ of microbes and dead cells
