9PFC

NSF, substrate free, hydrolyzing, class 26

Summary for 9PFC

• Entry DOI: 10.2210/pdb9pfc/pdb
• Related: 9OJ2 9OJJ 9OJR 9OJU 9OJZ 9OK3 9OK5 9OKC 9OLJ 9OLO 9OM6 9OMQ 9PAF 9PAG 9PB9 9PBA 9PBF 9PBV 9PC3 9PCX 9PCZ 9PD1 9PD8 9PDD 9PF2
• EMDB information: 71598
• Descriptor: Vesicle-fusing ATPase, ADENOSINE-5'-TRIPHOSPHATE, ADENOSINE-5'-DIPHOSPHATE, ... (6 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)
• Total number of polymer chains: 6
• Total formula weight: 503536.64

Authors

White, K.I.,Brunger, A.T. (deposition date: 2025-07-03, release date: 2025-10-08)

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.
Structural remodeling of target-SNARE protein complexes by NSF enables synaptic transmission.
Nat Commun, 16:8371-8371, 2025

PubMed Abstract: Synaptic vesicles containing neurotransmitters fuse with the plasma membrane upon the arrival of an action potential at the active zone. 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 reveal mechanistic details of AAA+ protein NSF (N-ethylmaleimide sensitive factor) and SNAP (soluble NSF attachment protein) action before fusion. We show that syntaxin clusters are conserved, that NSF colocalizes with them, and characterize SNARE populations that may exist within or near them using cryo-EM. Supercomplexes of NSF, α-SNAP, and either a syntaxin tetramer or one of 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: 40993127
DOI: 10.1038/s41467-025-62764-0

Experimental method

ELECTRON MICROSCOPY (3.15 Å)