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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.
