6CO2

Structure of an engineered protein (NUDT16TI) in complex with 53BP1 Tudor domains

6CO2 の概要

• エントリーDOI: 10.2210/pdb6co2/pdb
• 関連するPDBエントリー: 6CO1
• 分子名称: NUDT16-Tudor-interacting (NUDT16TI), TP53-binding protein 1 (3 entities in total)
• 機能のキーワード: designer protein, engineered protein, nudt16ti, nudt16, 53bp1, tirr, tudor domain, rna binding, protein binding, rna nucleotide diphosphatase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 70970.90

構造登録者

Botuyan, M.V.,Thompson, J.R.,Cui, G.,Mer, G. (登録日: 2018-03-10, 公開日: 2018-06-06, 最終更新日: 2023-10-04)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.49 Å)