Lecture 3 Flashcards
Where is the main starting location of protein synthesis?
The cytosol
Where do proteins enter the ER through?
The rough Endoplasmic reticulum by binding to Sec61
Where do proteins leave the ER?
Through the smooth ER
Is protein translocation co-translational or post-translational?
Co-translational mediated by SRP
What features do secreted proteins have in common?
Stretch of 10 - 15 hydrophobic amino acids.
One or more positively charged residue preceding the hydrophobic sequence.
A short polar sequence at the carboxyl terminus of the hydrophobic stretch that is relatively polar with short side chains near cleavage site.
Are all Signal peptides cleaved?
No, some signal peptides act as the single hydrophobic domain of the protein. This is especially true in many multipass membrane proteins.
What is the SRP protein?
SRP proteins contain 6 protein subunits and 1 RNA molecule.
The SRP protein facilitates translocation of nascent polypeptides in the process of being produced to the rough ER.
How is SRP function regulated by GTP?
SRP and its receptor (SRP receptor) can both individually bind GTP. However, each has only half the catalytic site needed for GTP hydrolysis. Binding to GTP will activate SRP, where it then binds to the protein-ribosome complex (specifically), and then to its receptor on Sec61. Once bound, GTP is hydrolysed, the protein-ribosome complex is transferred to Sec61 complex and given GTP is now GDP, it will dissociate.
How does the SRP-ribosome complex “know” where to start producing the protein?
The SRP-ribosome complex docks onto an SRP receptor and then GTP is hydrolysed causing the channel (Sec61) underneath it to open up, revealing a hydrophilic pore for the protein.
Where does GTP hydrolysis takes place in the SRP-receptor interaction?
Both the SRP and the receptor hydrolyse GTP.
Individually, they bind GTP, but individually cannot hydrolyse. Only the SRP-SRP receptor complex can.
what is the name of the protein channel through which proteins are translocated in the ER?
Sec61
What is the structure of Sec 61 like?
Sec61 is a trimer with alpha, beta, and gamma, subunits. and a seam that can open when Sec61 is in the “open” conformation. It forms a ring with a plug in the middle. Opening of the seam shunts the plug aside and reveals the hydrophilic pore.
How does Sec61 release proteins into the ER membrane?
Sec61 can open sideways to allow the hydrophobic chain to enter the membrane.
Does translation stop when the protein-ribosome complex is being transferred to Sec61 by SRP?
Yes, the SRP has a translational pause domain to allow docking to occur.
