Motions of the SecA protein motor bound to signal peptide: Insights from molecular dynamics simulations

摘要

Abstract SecA is an essential part of the Sec pathway for protein secretion in bacteria. In this pathway, SecA interacts with the N -terminal fragment of the secretory protein – the signal peptide, and couples binding and hydrolysis of adenosine triphosphate with movement of the secretory protein across the SecY protein translocon. How interactions with the signal peptide alter the conformational dynamics and long-distance conformational couplings of SecA is a key open question that we address here with molecular dynamics techniques. Analyses of protein motions indicate that the signal peptide alters SecA dynamics not only at the site where this peptide binds, but also at a nucleotide-binding domain. Hydrogen bond clusters contribute to the long-distance propagation of changes in SecA dynamics. Graphical abstract Display Omitted Highlights ? We use simulations to derive a model of B . subtilis SecA bound to signal peptide. ? Two-dimensional hydrogen-bond maps identify inter-domain hydrogen bonds. ? Groups at an inter-domain interface engage in dynamic hydrogen bonds. ? Presence of the signal peptide associates with perturbed hydrogen bonds. ? The signal peptide influences domain motions and inter-domain correlations.