5z78

Structure of TIRR/53BP1 complex

spinqualitylabelsall models 5z78, resolution 1.76Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5z78 is a 3 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.762Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TIRR_MOUSE Key regulator of TP53BP1 required to stabilize TP53BP1 and regulate its recruitment to chromatin. In absence of DNA damage, interacts with the tandem Tudor-like domain of TP53BP1, masking the region that binds histone H4 dimethylated at 'Lys-20' (H4K20me2), thereby preventing TP53BP1 recruitment to chromatin and maintaining TP53BP1 localization to the nucleus. Following DNA damage, ATM-induced phosphorylation of TP53BP1 and subsequent recruitment of RIF1 leads to dissociate NUDT16L1/TIRR from TP53BP1, unmasking the tandem Tudor-like domain and allowing recruitment of TP53BP1 to DNA double strand breaks (DSBs). Binds U8 snoRNA.[UniProtKB:Q9BRJ7] Publication Abstract from PubMed P53-binding protein 1 (53BP1) regulates the double-strand break (DSB) repair pathway choice. A recently identified 53BP1-binding protein Tudor-interacting repair regulator (TIRR) modulates the access of 53BP1 to DSBs by masking the H4K20me2 binding surface on 53BP1, but the underlying mechanism remains unclear. Here we report the 1.76-A crystal structure of TIRR in complex with 53BP1 tandem Tudor domain. We demonstrate that the N-terminal region (residues 10-24) and the L8-loop of TIRR interact with 53BP1 Tudor through three loops (L1, L3, and L1'). TIRR recognition blocks H4K20me2 binding to 53BP1 Tudor and modulates 53BP1 functions in vivo. Structure comparisons identify a TIRR histidine (H106) that is absent from the TIRR homolog Nudt16, but essential for 53BP1 Tudor binding. Remarkably, mutations mimicking TIRR binding modules restore the disrupted binding of Nudt16-53BP1 Tudor. Our studies elucidate the mechanism by which TIRR recognizes 53BP1 Tudor and functions as a cellular inhibitor of the histone methyl-lysine readers. Structural basis for recognition of 53BP1 tandem Tudor domain by TIRR.,Dai Y, Zhang A, Shan S, Gong Z, Zhou Z Nat Commun. 2018 May 29;9(1):2123. doi: 10.1038/s41467-018-04557-2. PMID:29844495 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA