7XSJ

The structure of the Mint1/Munc18-1/syntaxin-1 complex

Summary for 7XSJ

• Entry DOI: 10.2210/pdb7xsj/pdb
• Descriptor: Syntaxin-binding protein 1, Syntaxin-1A, Amyloid-beta A4 precursor protein-binding family A member 1 (3 entities in total)
• Functional Keywords: munc18-1, mint1-mid, syntaxin-1, the mint1-mid-munc18-1-syntaxin-1 complex, protein binding
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 3
• Total formula weight: 106613.91

Authors

Feng, W.,Li, W. (deposition date: 2022-05-14, release date: 2022-11-16, Last modification date: 2023-11-29)

Primary citation

Li, W.,Xing, Y.,Wang, Y.,Xu, T.,Song, E.,Feng, W.
A non-canonical target-binding site in Munc18-1 domain 3b for assembling the Mint1-Munc18-1-syntaxin-1 complex.
Structure, 31:68-77.e5, 2023

PubMed Abstract: As the prototype of Sec1/Munc18 (SM) family proteins, Munc18-1 can manipulate the distinct conformations of syntaxin-1 for controlling intracellular membrane fusion. The Munc18-1-interacting domain of Mint1 (Mint1-MID) binds to Munc18-1 together with syntaxin-1 to form a Mint1-Munc18-1-syntaxin-1 complex, but the mechanism underlying the complex assembly remains unclear. Here, we determine the structure of the Mint1-MID-Munc18-1-syntaxin-1 complex. Unexpectedly, Munc18-1 recognizes Mint1-MID and syntaxin-1 simultaneously via two opposite sites. The canonical central cavity between domains 1 and 3a of Munc18-1 embraces closed syntaxin-1, whereas the non-canonical basic pocket in domain 3b captures the acidic Mint1-MID helix. The domain 3b-mediated recognition of an acidic-helical motif is distinct from other target-recognition modes of Munc18-1. Mutations in the interface between domain 3b and Mint1-MID disrupt the assembly of the Mint1-Munc18-1-syntaxin-1 complex. This work reveals a non-canonical target-binding site in Munc18-1 domain 3b for assembling the Mint1-Munc18-1-syntaxin-1 complex.

PubMed: 36608665
DOI: 10.1016/j.str.2022.11.002

Experimental method

X-RAY DIFFRACTION (3.2 Å)