8ooi

Full composite cryo-EM map of p97/VCP in ADP.Pi state

spinqualitylabelsall models 8ooi, resolution 2.61Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ooi is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.61Å Ligands: ADP, ATP, K, MG, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The human enzyme p97 regulates various cellular pathways by unfolding hundreds of protein substrates in an ATP-dependent manner, making it an essential component of protein homeostasis and an impactful pharmacological target. The hexameric complex undergoes substantial conformational changes throughout its catalytic cycle. Here we elucidate the molecular motions that occur at the active site in the temporal window immediately before and after ATP hydrolysis by merging cryo-EM, NMR spectroscopy and molecular dynamics simulations. p97 populates a metastable reaction intermediate, the ADP.P(i) state, which is poised between hydrolysis and product release. Detailed snapshots reveal that the active site is finely tuned to trap and eventually discharge the cleaved phosphate. Signalling pathways originating at the active site coordinate the action of the hexamer subunits and couple hydrolysis with allosteric conformational changes. Our multidisciplinary approach enables a glimpse into the sophisticated spatial and temporal orchestration of ATP handling by a prototype AAA+ protein. Characterizing ATP processing by the AAA+ protein p97 at the atomic level.,Shein M, Hitzenberger M, Cheng TC, Rout SR, Leitl KD, Sato Y, Zacharias M, Sakata E, Schutz AK Nat Chem. 2024 Mar;16(3):363-372. doi: 10.1038/s41557-024-01440-0. Epub 2024 Feb , 7. PMID:38326645 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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