Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Session V Abstracts

Fold to Fuse: The F2F Code of SNAREs on Membranes Lukas Tamm . University of Virginia, Charlottesville, VA, USA.

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) mediate membrane fusion in intracellular membrane traffic. Cognate SNAREs on the surface of vesicles (v-SNAREs) and target membranes (t-SNAREs) assemble in a highly exothermic reaction to form an intertwined 4-helix bundle. The energy gained from this folding reaction is used to force membranes into close proximity, bend them, remove water between them, and ultimately merge them into a single membrane. But, how exactly does the SNARE folding machine perform work on membranes? In this presentation I will show how the structures of v- and t-SNAREs change upon assembling with each other and when zippering towards their respective membrane-spanning transmembrane domains. A surprising, but important result is that the starting conformations of SNAREs are different on membranes than in solution and, moreover, that they depend on membrane curvature. These factors modulate the energy gain upon folding and thus also the minimal number of SNAREs that is required for generating a single productive fusion pore. These results were obtained by a combination of NMR, EPR, and single molecule fluorescence spectroscopy experiments, which helped us with dissecting the inner workings of this highly specialized and rather exquisite molecular machine. Ellena, Liang, Wiktor, Cafiso, Jahn, Tamm (2009) Dynamic structure of lipid-bound synaptobrevin suggests a nucleation-propagation mechanism for trans-SNARE complex formation. Proc. Natl. Acad. Sci. USA 106:20306. Kiessling, Ahmed, Domanska, Holt, Jahn, Tamm (2013) Rapid calcium-regulated fusion of synaptic vesicles with reconstituted target SNARE membranes. Biophys. J. 104:1950. Liang, Kiessling, Tamm (2013) Prefusion solution NMR structure of neuronal SNARE syntaxin. Proc. Natl. Acad. Sci. USA 110:19384. Liang, Davidowski, Ellena, Tamm*, Cafiso* (2014) The SNARE motif of synaptobrevin exhibits an aqueous-interfacial partitioning that is modulated by membrane curvature. Biochemistry 53:1485.

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