Figure 5.

Co-translational ER translocation by Sec61 through the ER translocon. (a) Graphic description of co-translational ER insertion/translocation by the SRP-Sec61. The SP is handed over from SRP54-M and inserts head-on into primed Sec61, removing the plug, before rearranging in a hairpin with a N_in-C_out conformation. The SP is then accommodated at the lateral gate of Sec61. (b) Tomographic map of the translating ER translocon (EMDB-4315) [90]. TRAP is accommodated at the side of Sec61, its cytosolic portion interacting with the ribosome, its luminal portion close to the opening of the translocation channel. The oligosaccharyltransferase (OST) does not interact with SPs. (c,d) Open and closed conformations of Sec61, based on PDBs 3J7Q and 3JC2 [92,95]. Upon channel opening, the plug (green, seen from within the lumen facing the membrane) is removed and the vertical channel is opened. The lateral gate can now harbor the SS. (e–g) SP binding site at the lateral gate. The binding site is partially open to the ER lipid environment, partially formed by hydrophobic residues of helices α2 and α7.