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- Title
Complexin cross-links prefusion SNAREs into a zigzag array.
- Authors
Kümmel, Daniel; Krishnakumar, Shyam S; Radoff, Daniel T; Li, Feng; Giraudo, Claudio G; Pincet, Frederic; Rothman, James E; Reinisch, Karin M
- Abstract
Complexin prevents SNAREs from releasing neurotransmitters until an action potential arrives at the synapse. To understand the mechanism for this inhibition, we determined the structure of complexin bound to a mimetic of a prefusion SNAREpin lacking the portion of the v-SNARE that zippers last to trigger fusion. The 'central helix' of complexin is anchored to one SNARE complex, while its 'accessory helix' extends away at ~45° and bridges to a second complex, occupying the vacant v-SNARE binding site to inhibit fusion. We expected the accessory helix to compete with the v-SNARE for t-SNARE binding but found instead that the interaction occurs intermolecularly. Thus, complexin organizes the SNAREs into a zigzag topology that, when interposed between the vesicle and plasma membranes, is incompatible with fusion.
- Publication
Nature structural & molecular biology, 2011, Vol 18, Issue 8, p927
- ISSN
1545-9985
- Publication type
Journal Article
- DOI
10.1038/nsmb.2101