Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming

Xiaoyu Yang, Shen Wang, Yi Sheng, Mingshu Zhang, Wenjuan Zou, Lijie Wu, Lijun Kang, Jose Rizo-Rey, Rongguang Zhang, Tao Xu, Cong Ma

Research output: Contribution to journalArticle

67 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)547-554
Number of pages8
JournalNature Structural and Molecular Biology
Volume22
Issue number7
DOIs
StatePublished - Jul 9 2015

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Yang, X., Wang, S., Sheng, Y., Zhang, M., Zou, W., Wu, L., Kang, L., Rizo-Rey, J., Zhang, R., Xu, T., & Ma, C. (2015). Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming. Nature Structural and Molecular Biology, 22(7), 547-554. https://doi.org/10.1038/nsmb.3038