TRAP mediated conformational changes of the human Sec61 channel.

The integral membrane pore Sec61 catalyzes the translocation of many secretory precursor proteins into the endoplasmic reticulum, as well as the insertion of transmembrane proteins into the cell and organellar membranes. Precursor proteins that possess weak signal peptides frequently require presence of the accessory membrane protein TRAP. Structural biology has recently established that TRAP shares several contact sites with Sec61, though not by an extended binding interface. However, how TRAP mechanistically supports the translocation of precursor proteins is still partially unresolved. Here, atomistic molecular dynamics simulations revealed that TRAP binding keeps Sec61 in a partially opened state, with looser packing of its transmembrane helices. TRAP maintained a partially opened Sec61 lateral gate and pore ring, shifting the plug helix towards an open conformation. These observations corroborate the existing model of how TRAP may support translocation of client precursor proteins with weak signal peptides.