Protein targeting Flashcards
SRP Interaction
Cystolic ribosome synthesises signal sequence (N terminus)-> SRP recognises signal sequence-> SRP binds to SRP receptor on ER-> ribosome bound to ER-> protein guided through translocon into lumen-> signal sequence cleaved by signal peptidase, SRP recycled
How do membrane proteins remain in ER membrane? Example
Stop transfer sequences include 20-22 hydrophobic aa. They remain as transmembrane segments
Fate of proteins made by ER
Transport vesicles from ER-> cis region of GA-> moves bit by bit to trans region of GA-> secretory vesicles (continuous or stimulated)/ insertion into plasma membrane or lysosome
How are membrane proteins docked?
Protein on vesicle has V snare; PM has T snare-> vesicle is docked-> membrane fusion
Fate of proteins by free ribosomes
Cytoplasm/peroxisome/nucleus (folded)
Mitochondria (unfolded)
How proteins end up in mitochondria
Chaperone (HSP70) takes protein to mitochondria-> signal sequence binds to receptor protein-> diffusion to protein translocator contact site-> chaperone released; receptor protein released-> protein moves into matrix (through inner and outer membrane)-> signal sequence cleaved-> mature protein
How proteins end up in nucleus
Folded protein contains Nuclear localisation signal-> NLS binds to importin-> transferred through nuclear pore-> protein released-> importin binds to G-protein Ran, GTP hydrolysed-> importin released back into cytoplasmic
How proteins end up in lysosome
Lysosomal proteins are tagged with mannose-6-phosphate in golgi-> mannose-6-phosphate receptor in golgi directs proteins into transport vesicles-> vesicle becomes lysosome
NLS is made of…
PKKKRKV
Inclusion cell disease
Mutant N-acetylglucosamine-1-phosphotransferase enzyme-> mannose not phosphorylated-> enzymes are secreted; lysosomes engorged with undigested substrate-> slow growth/developmental defects/ death
