4PDP

Crystal structure of Rad53 kinase domain and SCD2

4PDP の概要

• エントリーDOI: 10.2210/pdb4pdp/pdb
• 関連するPDBエントリー: 4PDS
• 分子名称: Serine/threonine-protein kinase RAD53 (1 entity in total)
• 機能のキーワード: ser/thr kinase domain, n-lobe, c-lobe, activation segment exchange, transferase
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 76853.33

構造登録者

Wybenga-Groot, L.E.,Ho, C.S.,Ceccarelli, D.F.,Sicheri, F. (登録日: 2014-04-19, 公開日: 2014-05-28, 最終更新日: 2023-09-27)

主引用文献

Wybenga-Groot, L.E.,Ho, C.S.,Sweeney, F.D.,Ceccarelli, D.F.,McGlade, C.J.,Durocher, D.,Sicheri, F.
Structural basis of Rad53 kinase activation by dimerization and activation segment exchange.
Cell Signal., 26:1825-1836, 2014

PubMed Abstract: The protein kinase Rad53 is a key regulator of the DNA damage checkpoint in budding yeast. Its human ortholog, CHEK2, is mutated in familial breast cancer and mediates apoptosis in response to genotoxic stress. Autophosphorylation of Rad53 at residue Thr354 located in the kinase activation segment is essential for Rad53 activation. In this study, we assessed the requirement of kinase domain dimerization and the exchange of its activation segment during the Rad53 activation process. We solved the crystal structure of Rad53 in its dimeric form and found that disruption of the observed head-to-tail, face-to-face dimer structure decreased Rad53 autophosphorylation on Thr354 in vitro and impaired Rad53 function in vivo. Moreover, we provide critical functional evidence that Rad53 trans-autophosphorylation may involve the interkinase domain exchange of helix αEF via an invariant salt bridge. These findings suggest a mechanism of autophosphorylation that may be broadly applicable to other protein kinases.

PubMed: 24815189
DOI: 10.1016/j.cellsig.2014.05.004

実験手法

X-RAY DIFFRACTION (2.591 Å)