Complexin induces a conformational change at the membrane-proximal C-terminal end of the SNARE complex
Ucheor B Choi,
Minglei Zhao,
Yunxiang Zhang,
Ying Lai,
Axel T Brunger
Affiliations
Ucheor B Choi
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University, Stanford, United States; Department of Neurology and Neurological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, United States; Department of Photon Science, Howard Hughes Medical Institute, Stanford University, Stanford, United States; Department of Structural Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
Minglei Zhao
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University, Stanford, United States; Department of Neurology and Neurological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, United States; Department of Photon Science, Howard Hughes Medical Institute, Stanford University, Stanford, United States; Department of Structural Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
Yunxiang Zhang
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University, Stanford, United States; Department of Neurology and Neurological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, United States; Department of Photon Science, Howard Hughes Medical Institute, Stanford University, Stanford, United States; Department of Structural Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
Ying Lai
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University, Stanford, United States; Department of Neurology and Neurological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, United States; Department of Photon Science, Howard Hughes Medical Institute, Stanford University, Stanford, United States; Department of Structural Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University, Stanford, United States; Department of Neurology and Neurological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, United States; Department of Photon Science, Howard Hughes Medical Institute, Stanford University, Stanford, United States; Department of Structural Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
Complexin regulates spontaneous 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 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.
