2VXC

Structure of the Crb2-BRCT2 domain complex with phosphopeptide.

2VXC の概要

• エントリーDOI: 10.2210/pdb2vxc/pdb
• 関連するPDBエントリー: 2VXB
• 分子名称: DNA REPAIR PROTEIN RHP9, H2A1 PEPTIDE, PRASEODYMIUM ION, ... (4 entities in total)
• 機能のキーワード: brct, nucleus, cell cycle, dna damage, dna replication inhibitor, phosphoprotein, checkpoint signalling
• 由来する生物種: SCHIZOSACCHAROMYCES POMBE (FISSION YEAST); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 56172.33

構造登録者

Kilkenny, M.L.,Roe, S.M.,Pearl, L.H. (登録日: 2008-07-03, 公開日: 2008-08-12, 最終更新日: 2024-10-09)

主引用文献

Kilkenny, M.L.,Dore, A.,Roe, S.M.,Nestoras, K.,Ho, J.C.Y.,Watts, F.Z.,Pearl, L.H.
Structural and Functional Analysis of the Crb2-Brct2 Domain Reveals Distinct Roles in Checkpoint Signaling and DNA Damage Repair.
Genes Dev., 22:2034-, 2008

PubMed Abstract: Schizosaccharomyces pombe Crb2 is a checkpoint mediator required for the cellular response to DNA damage. Like human 53BP1 and Saccharomyces cerevisiae Rad9 it contains Tudor(2) and BRCT(2) domains. Crb2-Tudor(2) domain interacts with methylated H4K20 and is required for recruitment to DNA dsDNA breaks. The BRCT(2) domain is required for dimerization, but its precise role in DNA damage repair and checkpoint signaling is unclear. The crystal structure of the Crb2-BRCT(2) domain, alone and in complex with a phosphorylated H2A.1 peptide, reveals the structural basis for dimerization and direct interaction with gamma-H2A.1 in ionizing radiation-induced foci (IRIF). Mutational analysis in vitro confirms the functional role of key residues and allows the generation of mutants in which dimerization and phosphopeptide binding are separately disrupted. Phenotypic analysis of these in vivo reveals distinct roles in the DNA damage response. Dimerization mutants are genotoxin sensitive and defective in checkpoint signaling, Chk1 phosphorylation, and Crb2 IRIF formation, while phosphopeptide-binding mutants are only slightly sensitive to IR, have extended checkpoint delays, phosphorylate Chk1, and form Crb2 IRIF. However, disrupting phosphopeptide binding slows formation of ssDNA-binding protein (Rpa1/Rad11) foci and reduces levels of Rad22(Rad52) recombination foci, indicating a DNA repair defect.

PubMed: 18676809
DOI: 10.1101/GAD.472808

実験手法

X-RAY DIFFRACTION (3.1 Å)