9NVD
NSF Mg2+ class 2 hexamer
Summary for 9NVD
| Entry DOI | 10.2210/pdb9nvd/pdb |
| EMDB information | 49833 |
| Descriptor | Vesicle-fusing ATPase, ADENOSINE-5'-TRIPHOSPHATE, ADENOSINE-5'-DIPHOSPHATE (3 entities in total) |
| Functional Keywords | snare, nsf, sec18, aaa+, translocase |
| Biological source | Cricetulus griseus (Chinese hamster) |
| Total number of polymer chains | 6 |
| Total formula weight | 502943.59 |
| Authors | |
| Primary citation | Khan, Y.A.,White, K.I.,Pfuetzner, R.A.,Singal, B.,Esquivies, L.,Mckenzie, G.,Liu, F.,DeLong, K.,Choi, U.B.,Montabana, E.,Mclaughlin, T.,Wickner, W.T.,Brunger, A.T. SNARE disassembly requires Sec18/NSF side loading. Nat.Struct.Mol.Biol., 32:1708-1720, 2025 Cited by PubMed Abstract: SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor) proteins drive membrane fusion at different cell compartments as their core domains zipper into a parallel four-helix bundle. After fusion, these bundles are disassembled by the AAA+ (ATPase associated with diverse cellular activities) protein Sec18/NSF and its adaptor Sec17/α-SNAP to make them available for subsequent rounds of membrane fusion. SNARE domains are often flanked by C-terminal transmembrane or N-terminal domains. Previous structures of the NSF-α-SNAP-SNARE complex revealed binding to the D1 ATPase pore, posing a topological constraint as SNARE transmembrane domains would prevent complete substrate threading as suggested for other AAA+ systems. Using mass spectrometry in yeast cells, we show N-terminal SNARE domain interactions with Sec18, exacerbating this topological issue. We present cryo-electron microscopy (cryo-EM) structures of a yeast SNARE complex, Sec18 and Sec17 in a nonhydrolyzing condition, which show SNARE Sso1 threaded through the D1 and D2 ATPase rings of Sec18, with its folded, N-terminal Habc domain interacting with the D2 ring. This domain does not unfold during Sec18/NSF activity. Cryo-EM structures under hydrolyzing conditions revealed substrate-released and substrate-free states of Sec18 with a coordinated opening in the side of the ATPase rings. Thus, Sec18/NSF operates by substrate side loading and unloading topologically constrained SNARE substrates. PubMed: 40604310DOI: 10.1038/s41594-025-01590-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.7 Å) |
Structure validation
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