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 types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Vesicular Transport / chemistry*
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Adaptor Proteins, Vesicular Transport / metabolism
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Adaptor Proteins, Vesicular Transport / physiology
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Amino Acid Sequence
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Animals
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Binding Sites
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Crystallography, X-Ray
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Humans
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Membrane Fusion / physiology
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Models, Molecular
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Molecular Sequence Data
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Nerve Tissue Proteins / chemistry*
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Nerve Tissue Proteins / metabolism
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Nerve Tissue Proteins / physiology
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Protein Structure, Tertiary
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Rats
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Syntaxin 1 / chemistry
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Syntaxin 1 / metabolism
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Vesicle-Associated Membrane Protein 2 / chemistry*
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Vesicle-Associated Membrane Protein 2 / metabolism
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Vesicle-Associated Membrane Protein 2 / physiology
Substances
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Adaptor Proteins, Vesicular Transport
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Nerve Tissue Proteins
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Stx1a protein, rat
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Syntaxin 1
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VAMP2 protein, human
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Vesicle-Associated Membrane Protein 2
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complexin I
Associated data
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PDB/3RK2
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PDB/3RK3
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PDB/3RL0