ISDA: 6LPC

Deposition Date 2020-01-09

Release Date 2020-07-15

Last Version Date 2023-11-29

Entry Detail

PDB ID:

6LPC

Keywords:

EXOCYTOSIS

Title:

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

Biological Source:

Source Organism(s):

Rattus norvegicus (Taxon ID: 10116)

Expression System(s):

Escherichia coli bl21(de3)

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

3.40 Å

R-Value Free:

0.33

R-Value Work:

0.28

R-Value Observed:

0.28

Space Group:

P 41

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Macromolecular Entities

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:Syntaxin-binding protein 1
Gene (Uniprot):Stxbp1
Mutagens:K332E, K333E
Chain IDs:A, B
Chain Length:594
Number of Molecules:2
Biological Source:Rattus norvegicus

UniProt ID:P61765 Pfam ID:PF00995

Ligand Molecules

Primary Citation

Munc13 activates the Munc18-1/syntaxin-1 complex and enables Munc18-1 to prime SNARE assembly.

Wang, X, Gong, J, Zhu, L, Wang, S, Yang, X, Xu, Y, Yang, X, Ma, C.Show

EMBO J. 39 e103631 e103631 (2020)

PMID: 32643828 DOI: 10.15252/embj.2019103631

Abstact

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.

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Primary Citation of related structures

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