Andrew E. Blanchard, Mark J. Arcario, Klaus Schulten, and Emad Tajkhorshid.
A highly tilted membrane configuration for the pre-fusion state of
synaptobrevin.
Biophysical Journal, 107:2112-2121, 2014.
(PMC: PMC4223215)
BLAN2014
The SNARE complex plays a vital role in vesicle fusion arising during neuronal exocytosis.
Key components in the regulation of SNARE complex formation, and ultimately fusion, are
the transmembrane (TM) and linker regions of the vesicle associated protein,
synaptobrevin. However, the membrane embedded structure of synaptobrevin in its pre-
fusion state, which determines its interaction with other SNARE proteins during fusion, is
largely unknown. This study reports all-atom molecular dynamics simulations of the pre-
fusion configuration of synaptobrevin in a lipid bilayer, aimed at characterizing the
insertion depth and the orientation of the protein in the membrane, as well as the nature of
the amino acids involved in determining these properties. By characterizing the structural
properties of both wild type and mutant synaptobrevin, the effects of C-terminal additions
on tilt and insertion depth of membrane embedded synaptobrevin are determined. The
simulations suggest a robust, highly tilted state for membrane embedded synaptobrevin
with a helical connection between the TM and linker regions, leading to a new
characterization of structural elements in pre-fusion synaptobrevin and providing a
framework for interpreting past mutation experiments.
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