title: Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming.
abstract: UNC-13-Munc13s have a central function in synaptic-vesicle priming through their MUN domains. However, it is unclear whether this function arises from the ability of the MUN domain to mediate the transition from the Munc18-1-closed syntaxin-1 complex to the SNARE complex in vitro. The crystal structure of the rat Munc13-1 MUN domain now reveals an elongated, arch-shaped architecture formed by α-helical bundles, with a highly conserved hydrophobic pocket in the middle. Mutation of two residues (NF) in this pocket abolishes the stimulation caused by the Munc13-1 MUN domain on SNARE-complex assembly and on SNARE-dependent proteoliposome fusion in vitro. Moreover, the same mutation in UNC-13 abrogates synaptic-vesicle priming in Caenorhabditis elegans neuromuscular junctions. These results support the notion that orchestration of syntaxin-1 opening and SNARE-complex assembly underlies the central role of UNC-13-Munc13s in synaptic-vesicle priming.
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shen
authors.identifier: 0000000250131039
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Mingshu
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Neuroscience, Zhejiang University, Hangzhou, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zou
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Wu
authors.affiliation: Institute of Neuroscience, Zhejiang University, Hangzhou, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Kang
authors.affiliation: Department of Biophysics, Biochemistry and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Josep
authors.initials: J
authors.lastname: Rizo
authors.affiliation: 1] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. [2] Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Rongguang
authors.initials: R
authors.lastname: Zhang
authors.affiliation: 1] Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China. [2] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. [3] College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Ma
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D050600:SNARE Proteins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*; D050827:Syntaxin 1 / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; D050827:Syntaxin 1; C103912:Unc13a protein, rat