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

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Abstract

Complexin regulates spontaneous release and activates Ca²⁺-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 when 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. Together with a previous study involving αSNAP, these data suggest that the C-terminal end of the ternary SNARE complex is more plastic than the N-terminal half. 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.

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Ucheor B Choi

Departments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Photon Science, and Structural Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Minglei Zhao

Departments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Photon Science, and Structural Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Yunxiang Zhang

Departments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Photon Science, and Structural Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Ying Lai

Departments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Photon Science, and Structural Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Axel T Brunger

Departments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Photon Science, and Structural Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States

For correspondence
brunger@stanford.edu

Competing interests
Axel T Brunger, Reviewing editor, eLife.

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