Protein targeting Flashcards
Why is protein targeting important?
Cellular function compartmentalized Function defined by proteins Proteins have to be directed to different parts of the cell Organelles Membranes proteins Secreted proteins Cytosolic proteins
How are the proteins directed to different locations
Primary sequences
What proteins are directed to the ER via a signal peptide
Secreted proteins
Membrane proteins
Lysosomal proteins
What proteins are directed to organelles via other peptide signals?
Nuclear proteins
Mitochondrial protein
Peroxisomal proteins
Signal sequence with SRP interactions
Protein synthesis starts with cytosolic ribosome
Signal sequence, 1st part protein synthesized (N terminus)
Signal sequence recognized by SRP complex, binds to receptor on ER
Ribosome bound to ER
New protein guided through translocon in ER into lumen
Signal sequence cleaved via signal peptidase, SRP recycled
How can the membrane protein remain in the ER membrane?
Protein has hydrophobic start transfer sequence and hydrophobic stop transfer sequence
When the hydrophobic stop transfer sequence is reached in translocation channel
Translocation channel move away from transmembrane protein
The importance of ER in protein synthesis
Reach final destination through a series of intracellular transport steps
Transport via membrane vesicles
Proteins often further processed in vesicles
How is the ER and Golgi involved int protein targeting?
Proteins synthesized, folded modified in ER
Form vesicles, migrate and merge with cis golgi
Further protein maturation in golgi
Movement between cisterns via vesicles
In trans golgi, mature proteins packaged in vesicle fro compartments
Vesicles transported along specific cytoskeleton pathways
What are the different cytoskeleton pathways for vesicles?
Integral membrane proteins/membrane phospholipid
Continuous secretory pathway
Stimulated secretory pathway, stored vesicles
Lysosome formation, matured from vesicles
Targeting vesicles to specific compartments
Membrane proteins in transport vesicles end up in membrane
V snare and T snare are complementary
Both snares are complementary to each other
Proteins within vesicles secreted
Targeting proteins to mitochondria
Occurs after translation completed but before complete protein folding occurs
Protein complexed with chaperone => mitonchondria
Signal sequence attaches to receptor protein on outer mitochondrial membrane
Protein complex moves so the translocon aligns with the translocon on the inner mitochondrial membrane
Protein diffuse into the matrix, cleaved signal sequence
Targeting proteins to nucleus
Occurs after translation, folding completed in cytoplasm
Nuclear proteins contain Nuclear localization signal
PKKKRKKV
NLS binds to importin, transported through nuclear pore
Requires G protein Ran, hydrolysis of GTP
Exportin peforms reverse function, exporting proteins from nucleus
Targeting proteins to lysosomes
Lysosomal protein tagged with mannose-6-phosphate in golgi
Mannose-6-phosphate receptor in golgi directs proteins into transport vesicles
Vesicle becomes lysosomes after maturation
