AUTHOR=Snead David , Lai Alex L. , Wragg Rachel T. , Parisotto Daniel A. , Ramlall Trudy F. , Dittman Jeremy S. , Freed Jack H. , Eliezer David 

TITLE=Unique Structural Features of Membrane-Bound C-Terminal Domain Motifs Modulate Complexin Inhibitory Function

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 10 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2017.00154

DOI=10.3389/fnmol.2017.00154

ISSN=1662-5099

ABSTRACT=Complexin is a small soluble presynaptic protein that interacts with neuronal SNARE proteins in order to regulate synaptic vesicle exocytosis.  While the SNARE-binding central helix of complexin is required for both the inhibition of spontaneous fusion and the facilitation of synchronous fusion, the disordered C-terminal domain (CTD) of complexin is specifically required for its inhibitory function.  The CTD of worm complexin binds to membranes via two distinct motifs, one of which undergoes a membrane curvature dependent structural transition that is required for efficient inhibition of neurotransmitter release, but the conformations of the membrane-bound motifs remain poorly characterized.  Visualizing these conformations is required to clarify the mechanisms by which complexin-membrane interactions regulate its function.  Here we employ optical and magnetic resonance spectroscopy to precisely define the boundaries of the two CTD membrane-binding motifs and to characterize their conformations.  We show that the curvature dependent amphipathic helical motif features an irregular element of helical structure, likely a pi-bulge, and that this feature is important for complexin inhibitory function in vivo.