Molecules to cells Flashcards
What occurs to the nuclear envelope during the cell cycle?
It is disassembled and later reassembled via phosphorylation and dephosphorylation of nuclear pore proteins and lamins.
Origin of nuclear envelope and ER
Invagination of the plasma membrane into the cytosol
main difference between mitochondria, chloroplasts and golgi, ER and lysosomes.
mitochondria and chloroplasts arent part of the vesicular transport network
Co-translational translocation
Process by which proteins are threaded across the ER membrane during polypeptide synthesis
Main property of ER signal sequence
Made up of string of hydrophobic amino acids
Main property of Nuclear localisation signal sequence
made up of string of basic amino acids
stop-transfer sequence
signal on integral membrane proteins which enables them to be integrated into the membrane
ER targeting signal
Signal sequence on proteins which enables them to be sent to the ER.
What do N-terminal signal sequences, stop-transfer sequences and signal-anchor sequences all have in common?
Made from hydrophobic amino acids, which makes them all recognizable by Sec61 complex
protein modifications at ER
1) cleavage of signal sequence
2) Disulphide bond formation
3) glycosylation
Protein disulphide isomerase
catalyses disulphide bond formation inside the ER lumen and ensures correct and appropriate bonds form.
Glycan
oligosaccharide present in ER lumen which modifies proteins by N-linked glycosylation
Dolicol
Lipid donor which provides an anchor for preformed N-linked glycans at the ER membrane
N-glycosidic bond of N-glycosylation
Carbon atom of first N-acetylglucosamine sugar of glycan to the nitrogen atom of asparagine
co-translational translocation
when a protein is translocated whilst still being synthesised
BiP
Heavy chain binding protein that acts as a chaperone using ATP to promote protein folding
Calnexin
ER chaperone that specifically assists in folding of N-glycosylated proteins
Scramblases
Enzyme that mediates flip-flopping of newly made lipids from cytosolic side of ER membrane to luminal side.
if you remove the KDEL retention signal from the ER resident protein BiP it will be:
secreted from the cell
If you add a KDEL signal to the C-terminus of a secretory protein like insulin it will be:
Retained in the ER
What is a key function of the cis-golgi?
Protein sorting
Examples of proteins which are secreted unconventionally
FGF2
IL 1β
What sorts cargo entering the cell?
the endosome
What does the endocytic pathway do?
Deliver lipids and proteins to endosomes so they can be re-used
Pinocytosis
Non-selective uptake of fluid and small particles by endocytic vesicles
During LDL endocytosis, what occurs to the receptor following uptake in the endosome and why?
It dissociates from the LDL due to an acidic pH. it is then recycled to the cell surface.
Addition of a mannose-6-phosphate signal to a protein will result in it being:
- Retained at the ER
- Sorted to secretory vesicles
- Trafficked to the lysosome
Phagocytosis
Uptake of large particles and microorganisms by specialised cells such as macrophages
Autophagy
removal of obsolete parts of the cells and damaged organelles.
what enzyme catalyses the fusion of autophagosomes with lysosomes?
SNARE proteins
flippases
enzymes localised in golgi which selectively redistribute lipids in order to create specific phospholipid asymmetry across the bilayer
Peripheral membrane proteins
proteins associated with the plasma membrane via binding to an integral transmembrane protein
What is the route of protein destined for the plasma membrane?
ER -> golgi -> plasma membrane
Common features of mitochondrial signal sequences
High content of Arg and Ser/Thr
Tendency to form amphiphillic alpha helices
Congenital lactic acidosis
inherited metabolic disorder causes by a point mutation of residue 10 of pyruvate dehydrogenase subunit E1α, resulting in inefficient import of the pyruvate dehydrogenase complex causing reduced levels of PDH.
Precursor of insulin
preproinsulin
Types of preproinsulin mutation
Arg to Cys/His
Ala 24 converted to Asp
Arg to Cys/His preproinsulin mutation
Prevents signal sequence interacting with Sec61 translocon.
Protein accumulates in cytosol causing gradual aggregation and death of pancreatic beta cells.
Mutation which causes early onset diabetes
Ala24 to Asp
Ala24 to Asp preproinsulin mutation
Inhibits cleavage of signal sequence causing improper folding causing ER stress due to accummulation in ER lumen.
Blocks export of wild type insulin from ER.
Mutation which causes late onset diabetes
Arg to Cys/His
mylolactone is a polyketide toxin which acts to inhibit the :
Sec61 translocon
70% of cases of CF is caused by which mutation
The loss of a phenylalanine at residue 508 of CTFR - functions as a Cl- pump.
Molecular chaperones
Help proteins to fold correctly and prevent them from aggregating
BiP in the ER lumen is an example of a…
Molecular chaperone
What happens when a molecular chaperone is bonded for a prolonged period of time?
Causes mutant protein to be recognised as misfolded
What happens to misfolded proteins retained at the ER
They are eventually degraded by a ER associated degradation
Proteosomes and ubiquisination occurs within the ER lumen. TRUE/FALSE
Not present in ER lumen.
Only occurs in cytosol
THe most common form of CF is the result of a mutation that prevents
CFTR protein trafficking out of the ER
Effects of carbamazepine
Enhance the proteasomal and autophagic disposal of the α1-AT Z mutant - reducing the proteotoxic load on cells
Ways membrane bound organelles can import proteins
nuclear pores
translocation across membrane
vesicular transport
What is the role of adaptins?
Bind cargo receptors during formation of a transport vesicle
CM retention disease
preChylomicrons accumulate in the ER and are unable to reach the golgi
What causes chlomicron retention disease?
Defective Sar1 GTPase
what increases the risk of alzheimers disease
Cleavage of APP producing large and long amounts of A beta peptide
potential therapies for AD
Stop or reduce Aβ prod.
Reverse Aβ aggregation
