Opening the SecYEG Protein Translocon

Abstract

The Sec61/SecYEG translocon is the central component of the major biosynthetic pathway for membrane and secreted proteins. To incorporate membrane proteins into the endoplasmic reticulum membrane of eukaryotes (Sec61), or into the plasma membrane of prokaryotes (SecYEG), the translocon relies on the opening of a lateral helical gate formed by transmembrane (TM) helices TM2 and TM7. The crystallographic structure of the closed state of the translocon (B. van der Berg et al, Nature 427, 36-44, 2003) solved in the absence of bound signal peptide provides valuable information on possible scenarios of membrane protein insertion. Nevertheless, the sequence of structural rearrangements that leads to the opening of the translocon and the geometry of the translocon in its open state remain unknown. To derive information on the structure and dynamics of possible open conformations of the SecYEG translocon, we performed prolonged molecular dynamics simulations of the SecYEG translocon in which we mutated residues determined to participate in stabilizing interactions of the closed state. We have also performed a simulation of the SecYEG translocon with a bound signal peptide. The computations provide insights into interactions essential for keeping the lateral gate closed and how perturbations of these interactions cause rearrangements of the gate.This work was supported by research grants from the National Institute for General Medical Sciences, the NIH National Center for Research Resources, and the National Science Foundation.