9PC3

21bin20S complex (NSF-alphaSNAP-2:1 syntaxin-1a:SNAP-25), non-hydrolyzing, class 12

Summary for 9PC3

• Entry DOI: 10.2210/pdb9pc3/pdb
• Related: 9OJ2 9OJJ 9OJR 9OJU 9OJZ 9OK3 9OK5 9OKC 9OLJ 9OLO 9OM6 9OMQ 9PAF 9PAG 9PB9 9PBA 9PBF 9PBV
• EMDB information: 71496
• Descriptor: Vesicle-fusing ATPase, Syntaxin-1A, Synaptosomal-associated protein 25, ... (7 entities in total)
• Functional Keywords: atpase, snare, hydrolysis, disassembly, translocation, exocytosis, neurotransmitter release, synapse, synaptic transmission, membrane fusion, hydrolase
• Biological source: Cricetulus griseus (Chinese hamster); More
• Total number of polymer chains: 12
• Total formula weight: 690451.53

Authors

White, K.I.,Brunger, A.T. (deposition date: 2025-06-26, release date: 2025-08-06)

Primary citation

White, K.I.,Khan, Y.A.,Qiu, K.,Balaji, A.,Couoh-Cardel, S.,Esquivies, L.,Pfuetzner, R.A.,Diao, J.,Brunger, A.T.
Pre-fusion AAA+ remodeling of target-SNARE protein complexes enables synaptic transmission.
Biorxiv, 2024

PubMed Abstract: Membrane fusion is driven by SNARE complex formation across cellular contexts, including vesicle fusion during synaptic transmission. Multiple proteins organize trans-SNARE complex assembly and priming, leading to fusion. One target membrane SNARE, syntaxin, forms nanodomains at the active zone, and another, SNAP-25, enters non-fusogenic complexes with it. Here, we show that the AAA+ protein NSF (N-ethylmaleimide sensitive factor) and SNAP (soluble NSF attachment protein) must act prior to fusion. We show that syntaxin clusters are conserved, that NSF colocalizes with them, and characterize SNARE populations within and near these clusters using cryo-EM. Supercomplexes of NSF, α-SNAP, and either a syntaxin tetramer or two binary complexes of syntaxin-SNAP-25 reveal atomic details of SNARE processing and show how sequential ATP hydrolysis drives disassembly. These results suggest a functional role for syntaxin clusters as reservoirs and a corresponding role for NSF in syntaxin liberation and SNARE protein quality control preceding fusion.

PubMed: 39416070
DOI: 10.1101/2024.10.11.617886

Experimental method

ELECTRON MICROSCOPY (3.69 Å)