7lmy

Cryo-EM structure of human p97 in complex with NMS-873 in the presence of ATP, Npl4/Ufd1, and Ub6

spinqualitylabelsall models 7lmy, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.4Å Ligands: ATP, MG, Y6Y Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed p97 processes ubiquitinated substrates and plays a central role in cellular protein homeostasis. Here, we report a series of cryo-EM structures of the substrate-engaged human p97 complex with resolutions ranging from 2.9 to 3.8 A that captured 'power-stroke'-like motions of both the D1 and D2 ATPase rings of p97. A key feature of these structures is the critical conformational changes of the intersubunit signaling (ISS) motifs, which tighten the binding of nucleotides and neighboring subunits and contribute to the spiral staircase conformation of the D1 and D2 rings. In addition, we determined the cryo-EM structure of human p97 in complex with NMS-873, a potent p97 inhibitor, at a resolution of 2.4 A. The structures showed that NMS-873 binds at a cryptic groove in the D2 domain and interacts with the ISS motif, preventing its conformational change and thus blocking substrate translocation allosterically. Mechanistic insight into substrate processing and allosteric inhibition of human p97.,Pan M, Yu Y, Ai H, Zheng Q, Xie Y, Liu L, Zhao M Nat Struct Mol Biol. 2021 Jul;28(7):614-625. doi: 10.1038/s41594-021-00617-2., Epub 2021 Jul 14. PMID:34262183 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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