7yqk

cryo-EM structure of gammaH2AXK15ub-H4K20me2 nucleosome bound to 53BP1

spinqualitylabelsall models 7yqk, resolution 3.38Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7yqk is a 13 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.38Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function H4_HUMAN Publication Abstract from PubMed The chemical synthesis of homogeneously modified histones is a powerful approach to quantitatively decipher how post-translational modifications (PTMs) modulate epigenetic events. Herein, we describe the expedient syntheses of a selection of phosphorylated and ubiquitinated H2AX proteins in a strategy integrating expressed protein hydrazinolysis and auxiliary-mediated protein ligation. These modified H2AX proteins were then used to discover that although H2AXS139 phosphorylation can enhance the binding of the DNA damage repair factor 53BP1 to either an unmodified nucleosome or that bearing a single H2AXK15ub or H4K20me2 modification, it augments 53BP1's binding only weakly to nucleosomes bearing both H2AXK15ub and H4K20me2. To better understand why such a trivalent additive effect is lacking, we solved the cryo-EM structure (3.38 A) of the complex of 53BP1 with the H2AXK15ub/S139ph_H4K20me2 nucleosome, which showed that H2AXS139 phosphorylation distorts the interaction interface between ubiquitin and 53BP1's UDR motif. Our study revealed that there is redundancy in the interplay of multiple histone PTMs, which may be useful for controlling the dynamic distribution of effector proteins onto nucleosomes bearing different histone variants and PTMs in a time-dependent fashion, through specific cellular biochemical events. Chemical Synthesis of Post-Translationally Modified H2AX Reveals Redundancy in Interplay between Histone Phosphorylation, Ubiquitination, and Methylation on the Binding of 53BP1 with Nucleosomes.,Ai H, Chu GC, Gong Q, Tong ZB, Deng Z, Liu X, Yang F, Xu Z, Li JB, Tian C, Liu L J Am Chem Soc. 2022 Oct 12;144(40):18329-18337. doi: 10.1021/jacs.2c06156. Epub , 2022 Sep 27. PMID:36166692 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone 3D structures

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