9pf2 | pdb_00009pf2
NSF, substrate free, hydrolyzing, class 25
Structural highlights
FunctionNSF_CRIGR Required for vesicle-mediated transport. Catalyzes the fusion of transport vesicles within the Golgi cisternae. Is also required for transport from the endoplasmic reticulum to the Golgi stack. Seem to function as a fusion protein required for the delivery of cargo proteins to all compartments of the Golgi stack independent of vesicle origin. Interaction with AMPAR subunit GRIA2 leads to influence GRIA2 membrane cycling. Publication Abstract from PubMedSynaptic 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, alpha-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. Structural remodeling of target-SNARE protein complexes by NSF enables synaptic transmission.,White KI, Khan YA, Qiu K, Balaji A, Couoh-Cardel S, Esquivies L, Pfuetzner RA, Diao J, Brunger AT Nat Commun. 2025 Sep 24;16(1):8371. doi: 10.1038/s41467-025-62764-0. PMID:40993127[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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