3UEN

Crystal structure of TopBP1 BRCT4/5 domains

3UEN の概要

• エントリーDOI: 10.2210/pdb3uen/pdb
• 関連するPDBエントリー: 3UEO
• 分子名称: DNA topoisomerase 2-binding protein 1, THIOCYANATE ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: brct domain, phospho-peptide binding, peptide binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q92547
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22756.92

構造登録者

Leung, C.C.,Glover, J.N.M. (登録日: 2011-10-31, 公開日: 2013-07-03, 最終更新日: 2024-02-28)

主引用文献

Leung, C.C.,Sun, L.,Gong, Z.,Burkat, M.,Edwards, R.,Assmus, M.,Chen, J.,Glover, J.N.
Structural insights into recognition of MDC1 by TopBP1 in DNA replication checkpoint control.
Structure, 21:1450-1459, 2013

PubMed Abstract: Activation of the DNA replication checkpoint by the ATR kinase requires protein interactions mediated by the ATR-activating protein, TopBP1. Accumulation of TopBP1 at stalled replication forks requires the interaction of TopBP1 BRCT5 with the phosphorylated SDT repeats of the adaptor protein MDC1. Here, we present the X-ray crystal structures of the tandem BRCT4/5 domains of TopBP1 free and in complex with a MDC1 consensus pSDpT phosphopeptide. TopBP1 BRCT4/5 adopts a variant BRCT-BRCT packing interface and recognizes its target peptide in a manner distinct from that observed in previous tandem BRCT- peptide structures. The phosphate-binding pocket and positively charged residues in a variant loop in BRCT5 present an extended binding surface for the negatively charged MDC1 phosphopeptide. Mutations in this surface reduce binding affinity and recruitment of TopBP1 to γH2AX foci in cells. These studies reveal a different mode of phosphopeptide binding by BRCT domains in the DNA damage response.

PubMed: 23891287
DOI: 10.1016/j.str.2013.06.015

実験手法

X-RAY DIFFRACTION (1.9 Å)