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Elife. 2016 Jun 2;5. pii: e16886. doi: 10.7554/eLife.16886.

Complexin induces a conformational change at the membrane-proximal C-terminal end of the SNARE complex.

Choi UB1,2,3,4, Zhao M1,2,3,4, Zhang Y1,2,3,4, Lai Y1,2,3,4, Brunger AT1,2,3,4.

Author information

1
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University, Stanford, United States.
2
Department of Neurology and Neurological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, United States.
3
Department of Photon Science, Howard Hughes Medical Institute, Stanford University, Stanford, United States.
4
Department of Structural Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States.

Abstract

Complexin regulates spontaneous and activates Ca(2+)-triggered neurotransmitter release, yet the molecular mechanisms are still unclear. Here we performed single molecule fluorescence resonance energy transfer experiments and uncovered two conformations of complexin-1 bound to the ternary SNARE complex. In the cis conformation, complexin-1 induces a conformational change at the membrane-proximal C-terminal end of the ternary SNARE complex that specifically depends on the N-terminal, accessory, and central domains of complexin-1. The complexin-1 induced conformation of the ternary SNARE complex may be related to a conformation that is juxtaposing the synaptic vesicle and plasma membranes. In the trans conformation, complexin-1 can simultaneously interact with a ternary SNARE complex via the central domain and a binary SNARE complex consisting of syntaxin-1A and SNAP-25A via the accessory domain. The cis conformation may be involved in activation of synchronous neurotransmitter release, whereas both conformations may be involved in regulating spontaneous release.

KEYWORDS:

biophysics; calcium triggering; neuroscience; neurotransmitter release; rat; structural biology; synaptic vesicle fusion

PMID:
27253060
PMCID:
PMC4927292
DOI:
10.7554/eLife.16886
[Indexed for MEDLINE]
Free PMC Article

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