15.6:
Cotranslational Protein Translocation
Most proteins enter the ER lumen while still under synthesis — a process called cotranslational translocation.
First, the SRP-SRP receptor complex carrying the ribosome-nascent chain complex unloads it on the Sec61 channel.
Once the ribosome aligns with the channel, the signal sequence at the N terminal of the polypeptide chain latches onto a signal sequence recognition site.
As the translation continues, the polypeptide chain forms a loop pushing open the channel plug for entry into the ER lumen.
While the polypeptide descends into the lumen, the signal sequence exits through the lateral gate of the Sec61 channel to enter the adjacent signal peptidase complex, where it is cleaved off.
The channel plug remains pushed open as the protein passively descends into the ER lumen.
After complete protein translocation into the lumen, the channel plug bounces back to block the protein from returning to the cytosol.
Inside the ER lumen, resident ER chaperones like BiP immediately bind the translocated protein and assist in protein folding.
15.6:
Cotranslational Protein Translocation
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain into the lumen.
SRP mediates ribosome attachment to the Sec61 complex via the polypeptide exit tunnel of the large ribosomal subunit. The GTPase domains on both SRP and SR carry out GTP hydrolysis, which supports the transfer of the target polypeptide to the Sec61 channel. Subsequently, the ribosomes act as primary translocation motors and push the protein towards the ER lumen. Except for the GTPs spent during peptide chain elongation, no additional energy is expended for the protein to descend through the channel.
Accessory translocon complex proteins involved in cotranslational translocation
The translocating chain-associating membrane (TRAM) protein and translocon-associated protein (TRAP) complex are auxiliary components associated with the Sec61 channel during SRP-mediated translocation. The TRAP complex is a substrate-specific complex essential for secure anchoring of the signal sequences having low hydrophobicity. Its proteins directly interact with Sec61 and keep the channel in open confirmation to compensate for the weak interaction with the signal sequence.
On the other hand, TRAM is a membrane protein that acts as a chaperone. It assists in folding and membrane integration of cotranslationally translocating proteins.
Suggested Reading
- Mandon, Elisabet C., Steven F. Trueman, and Reid Gilmore. "Protein translocation across the rough endoplasmic reticulum." Cold Spring Harbor perspectives in biology 5, no. 2 (2013): a013342