Download MendeleySyntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming.
Yang, X., Wang, S., Sheng, Y., Zhang, M., Zou, W., Wu, L., Kang, L., Rizo, J., Zhang, R., Xu, T., Ma, C.(2015) Nat Struct Mol Biol 22: 547-554
- PubMed: 26030875
- DOI: https://doi.org/10.1038/nsmb.3038
- Primary Citation of Related Structures:
4Y21 - PubMed 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.
Organizational 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.
