5X6O

Intact ATR/Mec1-ATRIP/Ddc2 complex

Summary for 5X6O

• Entry DOI: 10.2210/pdb5x6o/pdb
• EMDB information: 6708
• Descriptor: Serine/threonine-protein kinase MEC1, DNA damage checkpoint protein LCD1 (2 entities in total)
• Functional Keywords: atr/mec1, kinase, dimeric, transferase, transferase-dna binding protein complex, transferase/dna binding protein
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Total number of polymer chains: 2
• Total formula weight: 360214.41

Authors

Wang, X.,Ran, T.,Cai, G. (deposition date: 2017-02-22, release date: 2017-12-20, Last modification date: 2024-10-30)

Primary citation

Wang, X.,Ran, T.,Zhang, X.,Xin, J.,Zhang, Z.,Wu, T.,Wang, W.,Cai, G.
3.9 angstrom structure of the yeast Mec1-Ddc2 complex, a homolog of human ATR-ATRIP.
Science, 358:1206-1209, 2017

PubMed Abstract: 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.

PubMed: 29191911
DOI: 10.1126/science.aan8414

Experimental method

ELECTRON MICROSCOPY (3.9 Å)