Complexin cross-links prefusion SNAREs into a zigzag array.

Publication Type:

Journal Article


Nat Struct Mol Biol, Volume 18, Issue 8, p.927-33 (2011)


Adaptor Proteins, Vesicular Transport, Amino Acid Sequence, Animals, Binding Sites, Crystallography, X-Ray, Humans, Membrane Fusion, Models, Molecular, Molecular Sequence Data, Nerve Tissue Proteins, Protein Structure, Tertiary, Rats, Syntaxin 1, Vesicle-Associated Membrane Protein 2


<p>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.</p>