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Regulation of Membrane Fusion by the Membrane-Proximal Coil of the t-SNARE during Zippering of SNAREpins

We utilize structurally targeted peptides to identify a " t C fusion switch" inherent to the coil domains of the neuronal t-SNARE that pairs with the cognate v-SNARE. The t C fusion switch is located in the membrane-proximal portion of the t-SNARE and controls the rate at which the helical...

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Bibliographic Details
Published in:The Journal of cell biology 2002-09, Vol.158 (5), p.929-940
Main Authors: Melia, Thomas J., Weber, Thomas, McNew, James A., Fisher, Lillian E., Johnston, Robert J., Parlati, Frank, Mahal, Lara K., Söllner, Thomas H., Rothman, James E.
Format: Article
Language:English
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Summary:We utilize structurally targeted peptides to identify a " t C fusion switch" inherent to the coil domains of the neuronal t-SNARE that pairs with the cognate v-SNARE. The t C fusion switch is located in the membrane-proximal portion of the t-SNARE and controls the rate at which the helical bundle that forms the SNARE-pin can zip up to drive bilayer fusion. When the fusion switch is "off" (the intrinsic state of the t-SNARE), zippering of the helices from their membrane-distal ends is impeded and fusion is slow. When the t C fusion switch is "on," fusion is much faster. The t C fusion switch can be thrown by a peptide that corresponds to the membrane-proximal half of the cognate v-SNARE, and binds reversibly to the cognate region of the t-SNARE. This structures the coil in the membrane-proximal domain of the t-SNARE and accelerates fusion, implying that the intrinsically unstable coil in that region is a natural impediment to the completion of zippering, and thus, fusion. Proteins that stabilize or destabilize one or the other state of the t C fusion switch would exert fine temporal control over the rate of fusion after SNAREs have already partly zippered up.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200112081