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Volume 10, Issue 8 (Suppl)

J Proteomics Bioinform, an open access journal

ISSN: 0974-276X

Structural Biology 2017

September 18-20, 2017

International Conference on

Structural Biology

September 18-20, 2017 Zurich, Switzerland

Protein machinery regulating the synaptic vesicle fusion

Maria Bykhovskaia

Wayne State University, USA

euronal transmitters are released

via

the fusion of synaptic vesicles with the plasma membrane. Vesicles dock to the

membrane

via

a protein complex termed SNARE, which contains membrane attached (t-SNARE) and vesicle attached

(v-SNARE) proteins. The fusion occurs in response to a calcium inflow, and the vesicle protein Synaptotagmin (Syt) serves

as a calcium sensor. A cytosolic protein Complexin (Cpx) interacts with the SNARE complex, restricting the spontaneous

fusion. Although molecular interactions of these proteins have been extensively studied, it is still debated how Syt dynamically

interacts with the SNARE protein complex, Cpx, and lipid bilayers to trigger lipid merging. To elucidate these mechanisms, we

combined molecular dynamics (MD) simulations with molecular biology and genetic approaches in

Drosophila

. Basing on MD

simulations, we created a model of the protein fusion machinery wherein Cpx dynamically interacts with v-SNARE, preventing

full SNARE assembly. Our MD simulations also elucidated how Syt interacts with lipid bilayers, causing lipid bulging that may

precede the formation of the stalk and the fusion pore opening. Finally, our simulations predicted direct interactions of Syt

with the SNARE-bound Cpx. The developed molecular model enabled us to predict new mutations in v-SNARE and Cpx that

alter the fusion process. To test these predictions, we generated

Drosophila

lines with single point mutations and investigated

how these mutations affect the kinetics of transmitter release. The results of these experiments suggest that our model creates

the basis for systematic approach to manipulating the fusion machinery based on theoretical predictions derived from MD

simulations.

Biography

Maria Bykhovskaia is an expert in synaptic transmission. Her lab combines molecular modeling and computations with electrophysiology, microscopy, and molecular

biology approaches. She holds a Professor’s position in the Washington State University. Her PhD training was in protein molecular modeling, and subsequently

she used a Postdoc in Computational Neuroscience to initiate a career devoted to the study of presynaptic mechanisms and plasticity. As a PI, she has developed

in her lab expertise in electrophysiology, live confocal imaging, and electron microscopy. The lab combines these experimental approaches with mathematical

modeling to understand the fundamental mechanisms of release of neuronal transmitters.

mbykhovs@med.wayne.edu

Maria Bykhovskaia, J Proteomics Bioinform 2017, 10:8(Suppl)

DOI: 10.4172/0974-276X-C1-0100