9n9s | pdb_00009n9s

Model of APC/C-CDC20-UBE2C from H3/H4-bound complex

spinqualitylabelsall models 9n9s, resolution 3.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9n9s is a 13 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 3.9Å Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function APC1_HUMAN Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. Publication Abstract from PubMed Non-degradative histone ubiquitylation plays a myriad of well-defined roles in the regulation of gene expression and choreographing DNA damage repair pathways. In contrast, the contributions of degradative histone ubiquitylation on genomic processes has remained elusive. Recently, the APC/C has been shown to ubiquitylate histones to regulate gene expression in pluripotent cells, but the molecular mechanism is unclear. Here we show that despite directly binding to the nucleosome through subunit APC3, the APC/C is unable to ubiquitylate nucleosomal histones. In contrast, extranucleosomal H2A/H2B and H3/H4 complexes are broadly ubiquitylated by the APC/C in an unexpected manner. Using a combination of cryo-electron microscopy (cryo-EM) and biophysical and enzymatic assays, we demonstrate that APC8 and histone tails direct APC/C-mediated polyubiquitylation of core histones in the absence of traditional APC/C substrate degron sequences. Taken together, our work implicates APC/C-nucleosome tethering in the degradation of diverse chromatin-associated proteins and extranucleosomal histones for the regulation of transcription and the cell cycle and for preventing toxicity due to excess histone levels. APC/C-mediated ubiquitylation of extranucleosomal histone complexes lacking canonical degrons.,Skrajna A, Bodrug T, Martinez-Chacin RC, Fisher CB, Welsh KA, Simmons HC, Arteaga EC, Simmons JM, Nasr MA, LaPak KM, Nguyen A, Huynh MT, Fargo I, Welfare JG, Zhao Y, Lawrence DS, Goldfarb D, Brown NG, McGinty RK Nat Commun. 2025 Mar 15;16(1):2561. doi: 10.1038/s41467-025-57384-7. PMID:40089476 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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