Membrane Binding Induces Distinct Structural Signatures in the Mouse Complexin-1C-Terminal Domain. Academic Article uri icon

Overview

abstract

  • Complexins play a critical role in regulating SNARE-mediated exocytosis of synaptic vesicles. Evolutionary divergences in complexin function have complicated our understanding of the role these proteins play in inhibiting the spontaneous fusion of vesicles. Previous structural and functional characterizations of worm and mouse complexins have indicated the membrane curvature-sensing C-terminal domain of these proteins is responsible for differences in inhibitory function. We have characterized the structure and dynamics of the mCpx1 CTD in the absence and presence of membranes and membrane mimetics using NMR, ESR, and optical spectroscopies. In the absence of lipids, the mCpx1 CTD features a short helix near its N-terminus and is otherwise disordered. In the presence of micelles and small unilamellar vesicles, the mCpx1 CTD forms a discontinuous helical structure in its C-terminal 20 amino acids, with no preference for specific lipid compositions. In contrast, the mCpx1 CTD shows distinct compositional preferences in its interactions with large unilamellar vesicles. These studies identify structural divergences in the mCpx1 CTD relative to the wCpx1 CTD in regions that are known to be critical to the wCpx1 CTD's role in inhibiting spontaneous fusion of synaptic vesicles, suggesting a potential structural basis for evolutionary divergences in complexin function.1.

publication date

  • June 28, 2022

Research

keywords

  • Adaptor Proteins, Vesicular Transport
  • Nerve Tissue Proteins
  • Unilamellar Liposomes

Identity

PubMed Central ID

  • PMC9794636

Scopus Document Identifier

  • 85134319067

Digital Object Identifier (DOI)

  • 10.1016/j.bpj.2017.04.002

PubMed ID

  • 35777466

Additional Document Info

volume

  • 435

issue

  • 1