6co1

Structure of human TIRR in complex with 53BP1 Tudor domains

spinqualitylabelsall models 6co1, resolution 2.18Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6co1 is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: NUDT16L1, SDOS, TIRR (HUMAN), TP53BP1 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [TP53B_HUMAN] Note=A chromosomal aberration involving TP53BP1 is found in a form of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;15)(q33;q22) with PDGFRB creating a TP53BP1-PDGFRB fusion protein. Function [TIRR_HUMAN] Key regulator of TP53BP1 required to stabilize TP53BP1 and regulate its recruitment to chromatin (PubMed:28241136). 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 (PubMed:28241136). 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) (PubMed:28241136). Binds U8 snoRNA (PubMed:18820299). [TP53B_HUMAN] Plays a key role in the response to DNA damage. May have a role in checkpoint signaling during mitosis. Enhances TP53-mediated transcriptional activation. Publication Abstract from PubMed Dynamic protein interaction networks such as DNA double-strand break (DSB) signaling are modulated by post-translational modifications. The DNA repair factor 53BP1 is a rare example of a protein whose post-translational modification-binding function can be switched on and off. 53BP1 is recruited to DSBs by recognizing histone lysine methylation within chromatin, an activity directly inhibited by the 53BP1-binding protein TIRR. X-ray crystal structures of TIRR and a designer protein bound to 53BP1 now reveal a unique regulatory mechanism in which an intricate binding area centered on an essential TIRR arginine residue blocks the methylated-chromatin-binding surface of 53BP1. A 53BP1 separation-of-function mutation that abolishes TIRR-mediated regulation in cells renders 53BP1 hyperactive in response to DSBs, highlighting the key inhibitory function of TIRR. This 53BP1 inhibition is relieved by TIRR-interacting RNA molecules, providing proof-of-principle of RNA-triggered 53BP1 recruitment to DSBs. Mechanism of 53BP1 activity regulation by RNA-binding TIRR and a designer protein.,Botuyan MV, Cui G, Drane P, Oliveira C, Detappe A, Brault ME, Parnandi N, Chaubey S, Thompson JR, Bragantini B, Zhao D, Chapman JR, Chowdhury D, Mer G Nat Struct Mol Biol. 2018 Jul 2. pii: 10.1038/s41594-018-0083-z. doi:, 10.1038/s41594-018-0083-z. PMID:29967538 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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