4Y21

Crystal Structure of Munc13-1 MUN domain

Summary for 4Y21

• Entry DOI: 10.2210/pdb4y21/pdb
• Descriptor: Protein unc-13 homolog A (1 entity in total)
• Functional Keywords: helical bundles, catchr, exocytosis
• Biological source: Rattus norvegicus (Rat)
• Cellular location: Cytoplasm: Q62768
• Total number of polymer chains: 1
• Total formula weight: 61987.02

Authors

Yang, X.Y.,Wang, S.,Sheng, Y.,Zhang, M.,Zou, W.J.,Wu, L.J.,Kang, L.J.,Rizo, J.,Zhang, R.G.,Xu, T.,Ma, C. (deposition date: 2015-02-09, release date: 2015-06-10, Last modification date: 2023-11-08)

Primary citation

Yang, X.,Wang, S.,Sheng, Y.,Zhang, M.,Zou, W.,Wu, L.,Kang, L.,Rizo, J.,Zhang, R.,Xu, T.,Ma, C.
Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming.
Nat.Struct.Mol.Biol., 22:547-554, 2015

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.

PubMed: 26030875
DOI: 10.1038/nsmb.3038

Experimental method

X-RAY DIFFRACTION (2.9 Å)