Sec61Translokon

Secs61 translocon, commonly referred to as the Sec61 channel, is the principal protein-conducting gateway in the endoplasmic reticulum (ER) membrane. It mediates the translocation of nascent polypeptides into the ER lumen and the integration of membrane proteins into the ER membrane. In eukaryotes the channel is formed by the Sec61 heterotrimer, with Sec61α providing the core pore and Sec61β and Sec61γ acting as accessory subunits that stabilize the complex and influence gating.

The Sec61 channel is strategically positioned at the ER–cytosol interface and engages with ribosomes during co-translational translocation. It can also participate in post-translational pathways in some organisms. The channel is normally kept closed by a plug domain and opens upon ribosome binding or signal peptide insertion, allowing the growing polypeptide to pass through into the ER lumen or laterally into the lipid bilayer. A lateral gate within the channel enables hydrophobic segments of membrane proteins to exit into the lipid phase, facilitating proper membrane insertion.

Evolutionarily, the eukaryotic Sec61 complex is homologous to the bacterial SecYEG translocon, which serves a related function in prokaryotes. In eukaryotes, Sec61 works in concert with other factors, including components of the signal recognition particle pathway and glycosylation machinery, to coordinate translocation with folding, quality control, and post-translational modifications.

Beyond its essential role in protein targeting, the Sec61 translocon participates in ER-associated degradation and quality-control pathways, acting as a conduit for surveillance and remodeling of secretory and membrane proteins within the secretory pathway.