6CO1

Structure of human TIRR in complex with 53BP1 Tudor domains

Summary for 6CO1

• Entry DOI: 10.2210/pdb6co1/pdb
• Descriptor: Tudor-interacting repair regulator protein, TP53-binding protein 1 (3 entities in total)
• Functional Keywords: dna damage response, dna repair, dna damage signaling, 53bp1, tirr, nudt16l1, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 120045.33

Authors

Cui, G.,Botuyan, M.V.,Mer, G. (deposition date: 2018-03-10, 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

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: 29967538
DOI: 10.1038/s41594-018-0083-z

Experimental method

X-RAY DIFFRACTION (2.179 Å)