Unique Structural Features of Membrane-Bound C-Terminal Domain Motifs Modulate Complexin Inhibitory Function
Year: 2017
Type: article
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.
Institutions: Weill Cornell Medicine, Cornell University
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
Funders: U.S. Department of Defense, W. M. Keck Foundation, Deutsche Forschungsgemeinschaft, National Institutes of Health, National Institute on Aging, National Institute of Mental Health, National Institute of General Medical Sciences, National Institute of Biomedical Imaging and Bioengineering, National Center for Research Resources, Office of Research Infrastructure Programs, National Institutes of Health
Awards: Analysis of synaptic protein dynamics, Electron Spin Relaxation in Model Membranes, G2980379754, Structure and Function of Complexin, Structure and function of alpha-synuclein, Biophysical Characterization of Complexin C-terminal Domain Lipid Interactions, G5472329822, G5584780205, G5794637836, Electron Spin Relaxation in Model Membranes, Structure and Function of Alpha-Synuclein, G747539493, 900 MHz NMR Spectrometer for Structural Biology, EXTRAMURAL RESEARCH FACILITIES CONSTRUCTION, National Biomedical Center for Advanced ESR Technology (ACERT), G8562585310
OpenAlex ID: W2617245765