5YZ0

Cryo-EM Structure of human ATR-ATRIP complex

5YZ0 の概要

• エントリーDOI: 10.2210/pdb5yz0/pdb
• EMDBエントリー: 6862
• 分子名称: Serine/threonine-protein kinase ATR, ATR-interacting protein (2 entities in total)
• 機能のキーワード: cryo-em, atr-atrip, dna damnage response, cell cycle
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 775394.89

構造登録者

Rao, Q.,Liu, M.,Tian, Y.,Wu, Z.,Wang, H.,Wang, J.,Xu, Y. (登録日: 2017-12-11, 公開日: 2018-01-31, 最終更新日: 2024-10-16)

主引用文献

Rao, Q.,Liu, M.,Tian, Y.,Wu, Z.,Hao, Y.,Song, L.,Qin, Z.,Ding, C.,Wang, H.W.,Wang, J.,Xu, Y.
Cryo-EM structure of human ATR-ATRIP complex.
Cell Res., 28:143-156, 2018

PubMed Abstract: ATR (ataxia telangiectasia-mutated and Rad3-related) protein kinase and ATRIP (ATR-interacting protein) form a complex and play a critical role in response to replication stress and DNA damage. Here, we determined the cryo-electron microscopy (EM) structure of the human ATR-ATRIP complex at 4.7 Å resolution and built an atomic model of the C-terminal catalytic core of ATR (residues 1 521-2 644) at 3.9 Å resolution. The complex adopts a hollow "heart" shape, consisting of two ATR monomers in distinct conformations. The EM map for ATRIP reveals 14 HEAT repeats in an extended "S" shape. The conformational flexibility of ATR allows ATRIP to properly lock the N-termini of the two ATR monomers to favor ATR-ATRIP complex formation and functional diversity. The isolated "head-head" and "tail-tail" each adopts a pseudo 2-fold symmetry. The catalytic pockets face outward and substrate access is not restricted by inhibitory elements. Our studies provide a structural basis for understanding the assembly of the ATR-ATRIP complex and a framework for characterizing ATR-mediated DNA repair pathways.

PubMed: 29271416
DOI: 10.1038/cr.2017.158

実験手法

ELECTRON MICROSCOPY (4.7 Å)