ATR-ATRIP complex / positive regulation of DNA-templated DNA replication / telomere maintenance via recombination / regulation of double-strand break repair / reciprocal meiotic recombination / nucleobase-containing compound metabolic process / nuclear chromosome / telomere maintenance via telomerase / signal transduction in response to DNA damage / telomere maintenance ...ATR-ATRIP complex / positive regulation of DNA-templated DNA replication / telomere maintenance via recombination / regulation of double-strand break repair / reciprocal meiotic recombination / nucleobase-containing compound metabolic process / nuclear chromosome / telomere maintenance via telomerase / signal transduction in response to DNA damage / telomere maintenance / DNA damage checkpoint signaling / establishment of protein localization / chromatin organization / chromosome / DNA recombination / DNA replication / damaged DNA binding / non-specific serine/threonine protein kinase / protein kinase activity / DNA repair / protein serine kinase activity / protein serine/threonine kinase activity / mitochondrion / ATP binding / nucleus / cytoplasm 類似検索 - 分子機能
UME domain / UME (NUC010) domain / Domain in UVSB PI-3 kinase, MEI-41 and ESR-1 / DNA damage checkpoint protein, Lcd1 / DNA damage checkpoint protein / : / FATC domain / PIK-related kinase, FAT / FAT domain / FATC ...UME domain / UME (NUC010) domain / Domain in UVSB PI-3 kinase, MEI-41 and ESR-1 / DNA damage checkpoint protein, Lcd1 / DNA damage checkpoint protein / : / FATC domain / PIK-related kinase, FAT / FAT domain / FATC / FATC domain / PIK-related kinase / FAT domain profile. / FATC domain profile. / Phosphatidylinositol 3- and 4-kinases signature 1. / Phosphatidylinositol 3/4-kinase, conserved site / Phosphatidylinositol 3- and 4-kinases signature 2. / Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily / Phosphoinositide 3-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinase / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic domain / Tetratricopeptide-like helical domain superfamily / Armadillo-type fold / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性
Serine/threonine-protein kinase MEC1 / DNA damage checkpoint protein LCD1 類似検索 - 構成要素
ジャーナル: Science / 年: 2017 タイトル: 3.9 Å structure of the yeast Mec1-Ddc2 complex, a homolog of human ATR-ATRIP. 著者: Xuejuan Wang / Tingting Ran / Xuan Zhang / Jiyu Xin / Zhihui Zhang / Tengwei Wu / Weiwu Wang / Gang Cai / 要旨: The ataxia telangiectasia-mutated and Rad3-related (ATR) kinase is a master regulator of DNA damage response and replication stress in humans, but the mechanism of its activation remains unclear. ATR ...The ataxia telangiectasia-mutated and Rad3-related (ATR) kinase is a master regulator of DNA damage response and replication stress in humans, but the mechanism of its activation remains unclear. ATR acts together with its partner ATRIP. Using cryo-electron microscopy, we determined the structure of intact Mec1-Ddc2 (the yeast homolog of ATR-ATRIP), which is poised for catalysis, at a resolution of 3.9 angstroms. Mec1-Ddc2 forms a dimer of heterodimers through the PRD and FAT domains of Mec1 and the coiled-coil domain of Ddc2. The PRD and Bridge domains in Mec1 constitute critical regulatory sites. The activation loop of Mec1 is inhibited by the PRD, revealing an allosteric mechanism of kinase activation. Our study clarifies the architecture of ATR-ATRIP and provides a structural framework for the understanding of ATR regulation.