title: Complexin induces a conformational change at the membrane-proximal C-terminal end of the SNARE complex.
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.
authors.affiliation: 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.
authors.forename: Ucheor B
authors.initials: UB
authors.lastname: Choi
authors.affiliation: 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.
authors.forename: Minglei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Yunxiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lai
authors.affiliation: 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.
authors.forename: Axel T
authors.identifier: 0000-0001-5121-2036
authors.initials: AT
authors.lastname: Brunger
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D050600:SNARE Proteins / Q000737:chemistry* / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000737:chemistry / Q000378:metabolism; D050827:Syntaxin 1 / Q000737:chemistry / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; D050825:Synaptosomal-Associated Protein 25; D050827:Syntaxin 1; C095992:complexin I
keywords: biophysics; calcium triggering; neuroscience; neurotransmitter release; rat; structural biology; synaptic vesicle fusion