4BMC

Crystal structure of s.pombe Rad4 BRCT1,2

4BMC の概要

• エントリーDOI: 10.2210/pdb4bmc/pdb
• 関連するPDBエントリー: 4BMD
• 分子名称: S-M CHECKPOINT CONTROL PROTEIN RAD4, CHLORIDE ION (3 entities in total)
• 機能のキーワード: replication, topbp1, dna damage checkpoint
• 由来する生物種: SCHIZOSACCHAROMYCES POMBE (FISSION YEAST)
• 細胞内の位置: Nucleus: P32372
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21484.63

構造登録者

Meng, Q.,Rappas, M.,Wardlaw, C.P.,Garcia, V.,Carr, A.M.,Oliver, A.W.,Du, L.L.,Pearl, L.H. (登録日: 2013-05-07, 公開日: 2013-10-09, 最終更新日: 2023-12-20)

主引用文献

Qu, M.,Rappas, M.,Wardlaw, C.P.,Garcia, V.,Ren, J.Y.,Day, M.,Carr, A.M.,Oliver, A.W.,Du, L.L.,Pearl, L.H.
Phosphorylation-Dependent Assembly and Coordination of the DNA Damage Checkpoint Apparatus by Rad4(Topbp1.).
Mol.Cell, 51:723-, 2013

PubMed Abstract: The BRCT-domain protein Rad4(TopBP1) facilitates activation of the DNA damage checkpoint in Schizosaccharomyces pombe by physically coupling the Rad9-Rad1-Hus1 clamp, the Rad3(ATR) -Rad26(ATRIP) kinase complex, and the Crb2(53BP1) mediator. We have now determined crystal structures of the BRCT repeats of Rad4(TopBP1), revealing a distinctive domain architecture, and characterized their phosphorylation-dependent interactions with Rad9 and Crb2(53BP1). We identify a cluster of phosphorylation sites in the N-terminal region of Crb2(53BP1) that mediate interaction with Rad4(TopBP1) and reveal a hierarchical phosphorylation mechanism in which phosphorylation of Crb2(53BP1) residues Thr215 and Thr235 promotes phosphorylation of the noncanonical Thr187 site by scaffolding cyclin-dependent kinase (CDK) recruitment. Finally, we show that the simultaneous interaction of a single Rad4(TopBP1) molecule with both Thr187 phosphorylation sites in a Crb2(53BP1) dimer is essential for establishing the DNA damage checkpoint.

PubMed: 24074952
DOI: 10.1016/J.MOLCEL.2013.08.030

実験手法

X-RAY DIFFRACTION (1.982 Å)