6D0L
Structure of human TIRR
Summary for 6D0L
Entry DOI | 10.2210/pdb6d0l/pdb |
Related | 6CO1 6CO2 |
Descriptor | Tudor-interacting repair regulator protein (2 entities in total) |
Functional Keywords | protein binding, rna binding, nudt16l1, 53bp1, dna damage response, dna double-strand break repair |
Biological source | Homo sapiens (Human) |
Total number of polymer chains | 2 |
Total formula weight | 46077.89 |
Authors | Cui, G.,Botuyan, M.V.,Mer, G. (deposition date: 2018-04-10, release date: 2018-06-06, Last modification date: 2023-10-04) |
Primary citation | Botuyan, M.V.,Cui, G.,Drane, P.,Oliveira, C.,Detappe, A.,Brault, M.E.,Parnandi, N.,Chaubey, S.,Thompson, J.R.,Bragantini, B.,Zhao, D.,Chapman, J.R.,Chowdhury, D.,Mer, G. Mechanism of 53BP1 activity regulation by RNA-binding TIRR and a designer protein. Nat. Struct. Mol. Biol., 25:591-600, 2018 Cited by PubMed Abstract: 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. PubMed: 29967538DOI: 10.1038/s41594-018-0083-z PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.97 Å) |
Structure validation
Download full validation report