The influence of cell membrane and SNAP25 linker loop on the dynamics and unzipping of SNARE complex.

Yi Shi,Yong Zhang,Jizhong Lou,Jiajie Diao

doi:10.1371/journal.pone.0176235

Abstract

The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is composed of three neuronal proteins VAMP2, Syntaxin and SNAP25, which plays a core role during the process of membrane fusion. The zipping assembly of the SNARE complex releases energies and drives the vesicle and cell membrane into close proximity. In this study, we use all-atom molecular dynamics simulations to probe the dynamics of SNARE and its unzipping process in the context of membrane at the atomistic details. Our results indicated that the NTD of SNARE core domain is relatively more stable than CTD, which is in agreement with previous experiments. More importantly, possible interactions between the linker loop (LL) region of SNAP25 and VAMP2 are observed, suggests that the LL region may facilitate VAMP2 binding and SNARE initiation. The forced unzipping of SNARE in the presence of membrane and LL of SNAP25 reveals the possible pathway for energy generation of SNARE zipping, provides information to understand how force may regulate the cooperativity between the membrane and the SNARE complex.

Highlights

The material exchanges across cell membranes or membrane-bounded organelles such as neural transmitter release and hormone secretion are mediated by the soluble N-ethylmaleimidesensitive factor attachment protein receptor (SNARE) complex[1,2,3]
SNARE complex formed at the junction of cell membrane and synaptic vesicles, the formation process may be affected by the presence of membrane
To check how the dynamics of SNARE is influenced by the membrane, we performed large-scale molecular dynamics (MD) simulations with the lipid membrane included

Summary

Introduction

The material exchanges across cell membranes or membrane-bounded organelles such as neural transmitter release and hormone secretion are mediated by the soluble N-ethylmaleimidesensitive factor attachment protein receptor (SNARE) complex[1,2,3]. This minimal neuronal exocytotic fusion machinery composes a four-helix bundle formed by trans-membrane protein vesicle-associated membrane protein 2 (VAMP2, called Synaptobrevin), plasma membrane protein Syntaxin and SNAP-25, VAMP2 and Syntaxin each provides one helix to the SNARE four helix bundle, and the other two helixes are contributed by SNAP-25 (Fig 1A). The influence of membrane and SNAP25 linker loop to SNARE unzipping design, data collection and analysis, decision to publish, or preparation of the manuscript

Methods

Results

Conclusion