Biophysical Society Thematic Meeting | Ascona, Switzerland

Liposomes, Exosomes, and Virosomes: From Modeling Complex Membrane Processes to Medical Diagnostics and Drug Delivery

Poster Abstracts

40-POS Board 20 Interaction of Complexin with SNARE Proteins Depends on the Lipid Environment of the Membrane Binyong Liang 1,2 , Alex J. Kreutzberger 1,2 , Volker Kiessling 1,2 , Rafal Zdanowicz 1,3 , David S. Cafiso 1,3 , Lukas K. Tamm 1,2 . 2 University of Virginia, Charlottesville, VA, USA, 3 University of Virginia, Charlottesville, VA, USA. 1 University of Virginia, Charlottesville, VA, USA, Fusion of synaptic vesicles with the presynaptic membrane is mediated by SNAREs and several SNARE-interacting proteins. Complexin is a soluble protein, which binds strongly to fully assembled neuronal SNARE complexes. Complexin is required for Ca2+-triggered fast fusion at nerve terminals; however, its mechanism of action remains elusive and controversial. Inhibitory and fusion-promoting effects have been reported and attributed to different domains of complexin. In addition, preferential binding of complexin to charged and highly curved membranes has been postulated to also contribute to its regulatory effect. We have used solution NMR and EPR spectroscopy, isothermal titration calorimetry, fluorescent anisotropy, and TIRF microscopy to probe multiple interactions between complexin and SNARE proteins in different complexes in a number of membrane-mimetic systems. Based on the molecular details revealed by NMR and EPR, and thermodynamic and kinetic measurements performed by ITC and fluorescence anisotropy, respectively, we present a model of how complexin effects SNARE-mediated membrane fusion in a physiological lipid environment.

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