6LPC

Crystal Structure of rat Munc18-1 with K332E/K333E mutation

Summary for 6LPC

• Entry DOI: 10.2210/pdb6lpc/pdb
• Descriptor: Syntaxin-binding protein 1 (1 entity in total)
• Functional Keywords: synaptic exocytosis, membrane fusion, snares-binding, exocytosis
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 2
• Total formula weight: 135331.14

Authors

Wang, X.P.,Gong, J.H.,Wang, S.,Zhu, L.,Yang, X.Y.,Xu, Y.Y.,Yang, X.F.,Ma, C. (deposition date: 2020-01-09, release date: 2020-07-15, Last modification date: 2023-11-29)

Primary citation

Wang, X.,Gong, J.,Zhu, L.,Wang, S.,Yang, X.,Xu, Y.,Yang, X.,Ma, C.
Munc13 activates the Munc18-1/syntaxin-1 complex and enables Munc18-1 to prime SNARE assembly.
Embo J., 39:e103631-e103631, 2020

PubMed Abstract: Priming of synaptic vesicles involves Munc13-catalyzed transition of the Munc18-1/syntaxin-1 complex to the SNARE complex in the presence of SNAP-25 and synaptobrevin-2; Munc13 drives opening of syntaxin-1 via the MUN domain while Munc18-1 primes SNARE assembly via domain 3a. However, the underlying mechanism remains unclear. In this study, we have identified a number of residues in domain 3a of Munc18-1 that are crucial for Munc13 and Munc18-1 actions in SNARE complex assembly and synaptic vesicle priming. Our results showed that two residues (Q301/K308) at the side of domain 3a mediate the interaction between the Munc18-1/syntaxin-1 complex and the MUN domain. This interaction enables the MUN domain to drive the opening of syntaxin-1 linker region, thereby leading to the extension of domain 3a and promoting synaptobrevin-2 binding. In addition, we identified two residues (K332/K333) at the bottom of domain 3a that mediate the interaction between Munc18-1 and the SNARE motif of syntaxin-1. This interaction ensures Munc18-1 to persistently associate with syntaxin-1 during the conformational change of syntaxin-1 from closed to open, which reinforces the role of Munc18-1 in templating SNARE assembly. Taken together, our data suggest a mechanism by which Munc13 activates the Munc18-1/syntaxin-1 complex and enables Munc18-1 to prime SNARE assembly.

PubMed: 32643828
DOI: 10.15252/embj.2019103631

Experimental method

X-RAY DIFFRACTION (3.402 Å)