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Complexin cross-links prefusion SNAREs into a zigzag array.

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Kümmel D, Krishnakumar SS, Radoff DT, Li F, Giraudo CG, Pincet F, Rothman JE, Reinisch KM
OpenAccess logo Nat Struct Mol Biol 18 927-33 (2011)
Related entries: 3rk2, 3rl0

Cited: 116 times
EuropePMC logo PMID: 21785414

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.

Reviews - 3rk3 mentioned but not cited (2)

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  2. Molecular Mechanisms of Fast Neurotransmitter Release. Brunger AT, Choi UB, Lai Y, Leitz J, Zhou Q. Annu Rev Biophys 47 469-497 (2018)

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Reviews citing this publication (28)

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  22. Vesicular Release of GABA by Mammalian Horizontal Cells Mediates Inhibitory Output to Photoreceptors. Hirano AA, Vuong HE, Kornmann HL, Schietroma C, Stella SL, Barnes S, Brecha NC. Front Cell Neurosci 14 600777 (2020)
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  25. On the difficulties of characterizing weak protein interactions that are critical for neurotransmitter release. Rizo J, David G, Fealey ME, Jaczynska K. FEBS Open Bio 12 1912-1938 (2022)
  26. Complexin Membrane Interactions: Implications for Synapse Evolution and Function. Lottermoser JA, Dittman JS. J Mol Biol 435 167774 (2023)
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Articles citing this publication (78)



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