8u3s

Structure of human TIRR in complex with VHH4 nanobodyStructure of human TIRR in complex with VHH4 nanobody

Structural highlights

8u3s is a 2 chain structure with sequence from Homo sapiens and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.85Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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).^[1] ^[2]

References

↑ Taylor MJ, Peculis BA. Evolutionary conservation supports ancient origin for Nudt16, a nuclear-localized, RNA-binding, RNA-decapping enzyme. Nucleic Acids Res. 2008 Oct;36(18):6021-34. doi: 10.1093/nar/gkn605. Epub 2008, Sep 27. PMID:18820299 doi:http://dx.doi.org/10.1093/nar/gkn605
↑ Drane P, Brault ME, Cui G, Meghani K, Chaubey S, Detappe A, Parnandi N, He Y, Zheng XF, Botuyan MV, Kalousi A, Yewdell WT, Munch C, Harper JW, Chaudhuri J, Soutoglou E, Mer G, Chowdhury D. TIRR regulates 53BP1 by masking its histone methyl-lysine binding function. Nature. 2017 Mar 9;543(7644):211-216. doi: 10.1038/nature21358. Epub 2017 Feb 27. PMID:28241136 doi:http://dx.doi.org/10.1038/nature21358

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Taylor MJ, Peculis BA. Evolutionary conservation supports ancient origin for Nudt16, a nuclear-localized, RNA-binding, RNA-decapping enzyme. Nucleic Acids Res. 2008 Oct;36(18):6021-34. doi: 10.1093/nar/gkn605. Epub 2008, Sep 27. PMID:18820299 doi:http://dx.doi.org/10.1093/nar/gkn605

[2] Drane P, Brault ME, Cui G, Meghani K, Chaubey S, Detappe A, Parnandi N, He Y, Zheng XF, Botuyan MV, Kalousi A, Yewdell WT, Munch C, Harper JW, Chaudhuri J, Soutoglou E, Mer G, Chowdhury D. TIRR regulates 53BP1 by masking its histone methyl-lysine binding function. Nature. 2017 Mar 9;543(7644):211-216. doi: 10.1038/nature21358. Epub 2017 Feb 27. PMID:28241136 doi:http://dx.doi.org/10.1038/nature21358

[1]

[2]