title: An electrostatically preferred lateral orientation of SNARE complex suggests novel mechanisms for driving membrane fusion.
abstract: Biological membrane fusion is a basic cellular process catalyzed by SNARE proteins and additional auxiliary factors. Yet, the critical mechanistic details of SNARE-catalyzed membrane fusion are poorly understood, especially during rapid synaptic transmission. Here, we systematically assessed the electrostatic forces between SNARE complex, auxiliary proteins and fusing membranes by the nonlinear Poisson-Boltzmann equation using explicit models of membranes and proteins. We found that a previously unrecognized, structurally preferred and energetically highly favorable lateral orientation exists for the SNARE complex between fusing membranes. This preferred orientation immediately suggests a novel and simple synaptotagmin-dependent mechanistic trigger of membrane fusion. Moreover, electrostatic interactions between membranes, SNARE complex, and auxiliary proteins appear to orchestrate a series of membrane curvature events that set the stage for rapid synaptic vesicle fusion. Together, our electrostatic analyses of SNAREs and their regulatory factors suggest unexpected and potentially novel mechanisms for eukaryotic membrane fusion proteins.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.forename: Lin-Chen
authors.initials: LC
authors.lastname: Gong
authors.forename: Sen-Fang
authors.initials: SF
authors.lastname: Sui
mesh_terms: D000595:Amino Acid Sequence; D008561:Membrane Fusion; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050600:SNARE Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: D050600:SNARE Proteins