2K2W

Second BRCT domain of NBS1

2K2W の概要

• エントリーDOI: 10.2210/pdb2k2w/pdb
• 分子名称: Recombination and DNA repair protein (1 entity in total)
• 機能のキーワード: brct domain, dna repair, cell cycle checkpoint, cell cycle
• 由来する生物種: Xenopus laevis (African clawed frog)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13237.32

構造登録者

Xu, C.,Cui, G.,Botuyan, M.,Mer, G. (登録日: 2008-04-14, 公開日: 2008-06-17, 最終更新日: 2024-05-29)

主引用文献

Xu, C.,Wu, L.,Cui, G.,Botuyan, M.V.,Chen, J.,Mer, G.
Structure of a second BRCT domain identified in the nijmegen breakage syndrome protein Nbs1 and its function in an MDC1-dependent localization of Nbs1 to DNA damage sites.
J.Mol.Biol., 381:361-372, 2008

PubMed Abstract: The Nijmegen breakage syndrome protein Nbs1 is a component of the MRN (Mre11-Rad50-Nbs1) complex, central to the DNA damage response. While Nbs1 is generally believed to encompass a forkhead-associated domain linked to a breast cancer C-terminal (BRCT) domain, to date there is no experimental information on its three-dimensional structure. Through nuclear magnetic resonance (NMR) three-dimensional structure determination, we demonstrate that there is a second BRCT domain (BRCT2) in Nbs1. The domain has the characteristic BRCT topology, but with a long insertion shown to be flexible by NMR relaxation measurements. In the absence of sequence similarity to other proteins, a search for structural analogs of BRCT2 returned the second BRCT domain of the tandem BRCT repeats of cell cycle checkpoint proteins MDC1 (mediator of DNA damage checkpoint protein 1) and BRCA1 (breast cancer protein 1), suggesting that like MDC1 and BRCA1, Nbs1 also possesses tandem BRCT domains with phosphoprotein binding ability. Structure-based single point mutations in human Nbs1 were evaluated in vivo and revealed that BRCT2 is essential for an MDC1-dependent relocalization of Nbs1 to DNA damage sites, most likely through a direct interaction of Nbs1 tandem BRCT domains with phosphorylated MDC1.

PubMed: 18582474
DOI: 10.1016/j.jmb.2008.05.087

実験手法

SOLUTION NMR