Additional Reading Summary BIOC0007 Protein trafficking Lodish textbook PDF

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Additional Reading Summary BIOC0007 Protein trafficking Lodish textbook...

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Additional Reading: Lodish -Small GTP binding protein ARF or SAR1 belonging to the GTP binding protein family control the polymerization of coat proteins, hydrolysis of GTP triggers disassembly of vesicle coats. -Rab proteins (also GTP binding protein) regulate the docking of the vesicle with a specific membrane SNARE complexes mediate fusion of vesicles Three or four SNARE proteins comprise the SNARE complex — generally syntaxin, VAMP and SNAP-25 homologs Together, these regions fold and bind to each other to form a parallel four-helix bundle Release of SNARE complexes via ATP hydrolysis alpha snap and NSF are not necessary for membrane fusion but for the regeneration of free SNARE proteins NSF associates with SNARE complexs with the aid of alpha SNAP. The bound NSF then hydrolyzes ATP, releasing sufficient energy to dissociate SNARE complexes Cystic fibrosis is caused by mutations in a protein called CFTR CFTR synthetised as an integral protein in the ER and transported to the Golgi mutation prevents transport of CFTR to the plasma membrane by blocking its packaging into COPII vesicles budding from ER COPI structure: coat is formed when from large cytosolic complexes called coatomers composed of 7 polypeptides ER contains several soluble proteins destined to the folding and modification of newly synthesized secretory proteins e.g. BiP an the enzyme protein disulfide isomerase. KDEL receptor trafficking

KDEL signal for ER resident proteins, it is both necessary and suffiecient for the targeting of protein to the ER KDEL signal is recognized and bound by KDEL receptor found transport vesicles shuttling between ER and cis Golgi proteins that are transported from ER back to the golgi have Lys XX sequence at the end of their Cterminal (KKXX) sorting signal, necessary and sufficient for incorporating membrane proteins into COPI vesicle for retrogade transport Processing of N linked oligosaccharie chains on glycoproteins within Golgi stacks 1. removal of 3 mannose residues in the cis Golgi 2. 3 N-acetylglucosamine are added (GlcNAc) residues are added 3. 2 more mannose residues are removed and a singe fructose is added 4. addition of 3 galactose residues 5. linkage of N-acetylneuramic acid to each galactose residues 6. transferase enzymes add sugars to oligosaccharide cisternal maturation compositio of individual cisterna changes as golgi resident proteins move from later to earlier golgi compartments clathrin vesicles dynamin regulates pinching off of clathrin coated vesicles hsc70 (chaperone protein) uses energy derived from hydrolysis to drive depolymerization of clathrin coat into trikelion M6P target soluble proteins to lysosomes clathrin vesicle containing M6P receptor and bound lysosomal enzymes bud from trans Golgi network, lose their coats and fuse with late endosome M6P receptors can bind M6P no less than 6 vesicles budding from late endosomes recycle M6P receptors back to trans Golgi netwrok

lysosomal storage disease is caused by absence of one or more lysosomal enzymes, undigested components accumulate in the lysosomes as large inclusions 1. I cell disease: cells from affected lack Nacetylglucosamine phosphotransferase mecessary fr formation of M6P sorting signal

STEPS 1. In the trans golgi network, proteins that have M6P sorting signal interact with M6P receptors in the membrane and are therefore directed into the clathrin vesicles 2. coat surrounding released vesicles is rapidly depolymerized 3. uncoated transport vesicle fuses with late endosomes

4. after phosphorylated enzymes dissociate from M6P receptors, late endosomes fuse with lysosomes 5. coat protein and M6P receptors are recycled...