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.