Module 1 - Organelles/Cell Machinery Flashcards
Proteins
cells functioning units, encoded by DNA translated from mRNA, structure determines function – structural, sensors, transporters, communication, signalling
Oligomers
proteins composed of more than one polypeptide chain
Transcription
in the nucleus, DNA ––> mRNA, catalysed by RNA polymerase
RNA splicing
Before RNA leaves the nucleus (during or after transcription, non coding introns are removed, exons are joined to form transcript, 5’ cap and 3’ polydenylation
Introns
Non coding sequences – removed in splicing
Exons
Coding sequence – joined in splicing to form transcript
Translation
In ribosome in cytoplasm: mRNA ––> amino acids (codons+anticodons) ––> polypeptide ––> protein,
N–terminus
beginning of a protein, the end of a polypeptide or protein that has a free amine group (–NH^2)
C–terminus
end of a protein, the end of a polypeptide or protein that has a free carboxyl group (–COOH)
Anterograde
secretory pathway, away from the cell body, exocytosis (COP II vesicle protein)
Retrograde
Uptake, endocytosis, moving backwards (COP I vesicle protein)
Protein turnover
the continual renewal or replacement of proteins, cells are not stable!!
Primary structure
sequence of amino acids, determines proteins shape and structure
Secondary structure
alpha helix or beta pleated sheet.
Structural motifs
combinations of secondary strucutres – ring finger, zinc finger
Tertiary structure
three dimensional fully folded shape of a protein, a single polypeptide chain backbone with one or more secondary structures
Quaternary structure
results of two or more proteins interacting
Dimerization
process of forming a macromolecular complex from two protein monomers
Oligomerization
process of forming a macromolecular complex from multiple protein monomer subunits
Dimer
macromolecular complex made up of two protein subunits
Macromolecular complexes
nanomachines comprising of multiple different protein subunits, built by subcomplexes around a core subunit, modular and flexible, more diverse/complex function than proteins + domains
Domains
distinct regions of tertiary protein structure – eg. globular, fibrous, transmembrane – larger than structural motifs, functional
Daltons (Da)
units to measure mass at molecular scale, proteins ––> kiloDaltons (kDa), protein complexes ––> megadaltons (MDA)
Svedberg (S)
units to measure size/shape, bigger molecule = greater svedberg unit, non standard and non linear
ATP
contains high energy phosphate bonds, energy is released when the terminal phosphate bond is broken (hydrolysis)
ATP hydrolysis
ATP ––> ADP
post–translational modification
covalent modifications that change protein structure after the protein has been synthesised, changes structure and function – regulation for trafficking or degradation etc
Phosphorylation
the addition of a phosphate group to a molecule catalysed by kinases (from ATP), example of a PTM
Kinase
an enzyme that catalyses the transfer of a phosphate group from ATP to a specified molecule
Ubiquitination
addition of one or more ubiquitin (regulatory protein – targeting for degradation) to lysine residues, example of a PTM
Ubiquitin
protein that is linked to other proteins as a way of marking the targeted protein for degradation by proteasomes.
Allosteric regulation
regulation of protein structure/function cause by non covalent binding by a ligand (eg. calcium, nucleotide, protein), interaction without chemically linking, eg. Ca 2+ and calmodulin
GTPase switch
Guanosine–triphosphate (GTP) binding changes structure to increase enzyme activity (switch on), GTPase activating protein (GAP) catalyses inactivation and turns the system off (GDP), Guanine Exchange Factor (GEF) switches on
GTPase activating protein (GAP)
increases GTPase activity, catalyses hydrolysis of GTP ––> GDP turning the system off
Guanine Exchange factor (GEF)
stimulates the release of (GDP) turning the system on
Polymerase
catalyses polymerization reactions such as the synthesis of DNA and RNA
Chaperonins
a protein complex that assists in the folding of other proteins, barrel shaped, driven by ATP hydrolysis
Hydrolysis
breaking down of polymers/complex molecules by the chemical addition of water
Kinesin
motor proteins in cellular transport (anterograde)
Proteasome
cuts peptide bonds for degradation, ubiquitin chains are used to recognise proteins
Nucleus
large membrane (inner + outer) enclosed organelle that encodes the majority of proteins in the cell, gene expression determines nature of cell and organism, highly dynamic
Perinuclear
around the nucleus
Nuclear lamina
a netlike meshwork of cytoskeletal protein filaments, adjacent to the inner membrane that maintains the shape of the nucleus by mechanically supporting the nuclear envelope
Nucleolus
sub–organelle within nucleoplasm, genetically defined structure with no membrane, formed in regions of rRNA, site of ribosomal biogenesis, hotspot of transcriptional activity
Chromatin
DNA + histone complex, repeating unit is nucleosomes, packages 2m on DNA, dynamic – structure determines function
Nucleosomes
DNA coiled around histones, repeating unit of chromatin
Acetylation
addition of acetyl group, causes chromatin to loosen/become less condensed ––> transcriptionally active/euchromatin
Euchromatin
less condensed, transcriptionally active chromatin
Unacetylated
highly condensed, transcriptionally inactive chromatin/heterochromatin
Heterochromatin
highly condensed, transcriptionally inactive chromatin/unacetylated
Histones
protein molecules around which DNA is tightly coiled in chromatin, can be targets of PTMS to determine gene expression
Nuclear Pore Complex (NPC)
Large multiprotein structure forming a channel through the nuclear envelope that allows selected molecules to move between nucleus and cytoplasm
Nucleoporins (Nups)
proteins that make up the nuclear pore complex – 30 different kinds, scaffold, linker, barrier + transport, cytoplasmic filaments
Localisation signals
functionally distinct amino acid sequences on protein cargo to allow import or export from the NPC and overcome size barrier – Import: Nuclear Localisation Sequence (NLS), Export: Nuclear Export Sequence (NES)
Nuclear Localisation Sequence (NLS)
amino acid sequence recognised by importin receptors to allow the import of protein cargo in the nucleus
Nuclear Export Sequence (NES)
amino acid sequence recognised by exportin receptors to allow the import of protein cargo out of the nucleus
Importins
nuclear import receptors, binding controlled by GTPase switch
Exportins
nuclear export receptors ––> cytoplasm, binding controlled by GTPase switch
Ran–GTP
binds importin causing it to dissociate from the cargo into the nucleus, GTP ––> GDP releases importin , binding to exportins promotes association with cargo, GTP ––> GDP releases exportin
Ran–GDP
formed after Ran–GTP hydrolyses itself in the cytosol, dissociated from the receptor (exportin or importin)
Laminopathies
genetic mutations impacting lamins/nuclear membranes and proteins, nuclear and genome instability ––> premature ageing (HGPS)
Endoplasmic Reticulum (ER)
large continuous membrane, smooth and rough, protein modification – folding/quality control/glycosylation, secretory pathway, dynamic microtubule extension and retraction movement
Protein secretory pathway
ER ––> Golgi ––> Vesicle ––> Plasma membrane
Rough ER
sheet like cisternae flattened membrane, studded with ribosomes
Smooth ER
branched, tubular membrane of the ER
Reticulons
proteins responsible for ER membrane’s curvature, inserted in phospholipid bilayer to shape tubes
Lumen
area enclosed by the endoplasmic reticulum membrane, network of membrane tubules, vesicles and cisternae
Cotranslational translocation
during translation secretory protein polypeptide chains enter the ER bound to ribosomes, uses Singal Recognition Particple (SRP), SRP receptor at ER and translocon, polypeptide folds within ER lumen
Translocon
protein complex that transports polypeptides with a targeting signal sequence into the lumen of the endoplasmic reticulum ER from the cytosol
Type 1 membrane protein
protein translocated to ER, inserted into membrane using a stop–transfer anchor sequence, STA in embedded in lipid bilayer, cytoplasmic C–terminus and luminal N–terminus
Type 2 membrane protein
protein translated in cytoplasm then translocated to ER, signal anchor sequence embedded into lipid bilayer, reverse topology to type 1, cytoplasmic N–terminus and luminal C–terminus
Type 3 membrane protein
protein with same topology as type I but translocation mechanism is similar to type II, recognized by SRP, brought to translocon and anchored into membrane but in reverse orientation to Type II – same as type 1
Type 4 membrane protein
multiple stop–transfer anchor and signal–anchor sequences and combination of Type I, II and III mechanisms, tail anchored proteins, C–terminal anchor sequence is inserted into the membrane after translation
Glycosylation
post translational sugar modification of proteins, addition of sugar chains (glycans) to form glycoproteins, aids in folding and determines function
Glycoproteins
proteins that have carbohydrates/glycans covalently bonded to them
Golgi apparatus
ribbon like organelle, modifies/processes and packages proteins for export, glycosylation
Cisternae
Flattened, membrane disks that make up the golgi apparatus, cis, medial, trans, each contain different enzymes, cisternal maturation
Cis golgi network
section of the golgi apparatus that receives materials from the endoplasmic reticulum
trans golgi network
section of the golgi apparatus where proteins are segregated into different types of membrane enclosed vesicles for delivery to the plasma membrane or organelles
medial cisternae
section of the golgi apparatus between the cis and trans cisternae
GRASPs
golgi reassembly and stacking proteins, membrane associated proteins, dimerise and oligomerise, holds parallel cisternae
Golgins
coiled rod like proteins tethering of stacks of ribbons in golgi apparatus
COP II
vesicular trafficking protein – ER ––> cis Golgi (anterograde)
COP I
reverse vesicular trafficking protein, return– golgi ––> ER (retrograde)
Cisternal maturation
cisterane matures to trans face (cis ––> medial ––> trans), secretory cargo remains stationary, retrograde (COP II) transport maintains cisternal residency for membrane specific enzymes
Mitcochondria
multi membrane organelle, aerobic oxidation – glucose ––> ATP
Endosymbiosis
theory that mitochondria evolved from bacteria, mitochondria undergo fission like bacteria
mtDNA
mitochondrial DNA
Mitochondrial proteins
coded in mtDNA and nucleus, imported unfolded and folds in mitochondria lumen, with an N terminus targeting sequence recognised by an outer membrane receptor, passes through outer and inner membrane translocons simultaneously
Mitochondrial matrix
the compartment of the mitochondrion enclosed by the inner membrane and containing enzymes and substrates for the citric acid cycle, as well as ribosomes and DNA
Oxidative phosphorylation
The production of ATP using energy redox reactions of an electron transport chain, converts energy stored in hydrocarbon bonds of sugars (glucose) and lipids into ATP
Oxidation
loss of electrons
Reduction
gain of electrons
NADH
the reduced form of NAD+; an electron–carrying molecule that functions in cellular respiration
FADH
reduced form of FAD, electron carrying molecule that functions in cellular respiration
Glycolysis
glucose is converted to pyruvate (+NADH), occurs in the cytoplasm before the krebs cycle in the mitochondira
Cellular respiration
glycolysis, krebs cycle/citric acid cycle, oxidative phosphorylation (electron transport chain + chemiosmosis), glucose + oxygen ––> carbon dioxide + water + ATP
Pyruvate
end product of glycolysis, oxidised to Acetyl CoA and CO2
Acetyl CoA
Acetyl coenzyme A; the entry compound for the citric acid cycle in cellular respiration, formed from oxidising pyruvate
Citric Acid Cycle (Krebs Cycle)
second stage of cellular respiration, in which pyruvate/pyruvic acid is broken down into carbon dioxide in a series of energy–extracting reactions
Electron transport chain
A sequence of electron carrier molecules (membrane proteins) that shuttle electrons during the redox reactions that release energy used to make ATP.
Chemiosmosis
gradient created by H+ ions diffusing across semi–permeable membranes in the mitochondria, creates kinetic energy to drive ATP synthase to catalyse the phosphorylation to ADP to ATP
Mitochondrial fission
Mitochondrial fission factors (MFF) recruit G proteins that hydrolyse GTP to pinch membranes, used to segregated and remove damaged components to target for degradation
Mitochondrial fusion
Mitofusins (MFNS) G proteins hydrolyse– outer membrane followed by inner, used for growth and replication – segregation during cell division
Parkinson’s
mutations on genes encoding PINK kinase and a parkin – a ubiquitin ligase, required to prevent fusion of damaged mitochondria, therefore damaged organelles are not removed
G proteins
guanine nucleotide–binding proteins, family of proteins that act as molecular switches, involved in transmitting signals for movement in and out of cells
