【多选题】How are soluble proteins made on the ER released into the ER lumen?
A.
Two protein components help guide ER signal sequences to the ER membrane: (1) a signal-recognition particle (SRP), present in the cytosol, binds to both the ribosome and the ER signal sequence as it emerges from the ribosome; and (2) an SRP receptor, embedded in the ER membrane, recognizes the SRP. Binding of an SRP to a ribosome that displays an ER signal sequence slows protein synthesis by that ribosome until the SRP engages with an SRP receptor on the ER.
B.
Once bound, the SRP is released, the receptor passes the ribosome to a protein translocator in the ER membrane, and protein synthesis recommences. The polypeptide is then threaded across the ER membrane through a channel in the translocator. The SRP and SRP receptor thus function as molecular matchmakers, bringing together ribosomes that are synthesizing proteins with an ER signal sequence and protein translocators within the ER membrane.
C.
In addition to directing proteins to the ER, the signal sequence—which for soluble proteins is almost always at the N-terminus, the end synthesized first—functions to open the protein translocator. This sequence remains bound to the translocator, while the rest of the polypeptide chain is threaded through the membrane as a large loop.
D.
The signal sequence is removed by a transmembrane signal peptidase, which has an active site facing the lumenal side of the ER membrane. The cleaved signal sequence is then released from the protein translocator into the lipid bilayer and rapidly degraded. Once the C-terminus of a soluble protein has passed through the translocator, the protein is released into the ER lumen.