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-Structure paper
Title | Structure of the intact ATM/Tel1 kinase. |
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Journal, issue, pages | Nat Commun, Vol. 7, Page 11655, Year 2016 |
Publish date | May 27, 2016 |
Authors | Xuejuan Wang / Huanyu Chu / Mengjuan Lv / Zhihui Zhang / Shuwan Qiu / Haiyan Liu / Xuetong Shen / Weiwu Wang / Gang Cai / |
PubMed Abstract | The ataxia-telangiectasia mutated (ATM) protein is an apical kinase that orchestrates the multifaceted DNA-damage response. Normally, ATM kinase is in an inactive, homodimer form and is transformed ...The ataxia-telangiectasia mutated (ATM) protein is an apical kinase that orchestrates the multifaceted DNA-damage response. Normally, ATM kinase is in an inactive, homodimer form and is transformed into monomers upon activation. Besides a conserved kinase domain at the C terminus, ATM contains three other structural modules, referred to as FAT, FATC and N-terminal helical solenoid. Here we report the first cryo-EM structure of ATM kinase, which is an intact homodimeric ATM/Tel1 from Schizosaccharomyces pombe. We show that two monomers directly contact head-to-head through the FAT and kinase domains. The tandem N-terminal helical solenoid tightly packs against the FAT and kinase domains. The structure suggests that ATM/Tel1 dimer interface and the consecutive HEAT repeats inhibit the binding of kinase substrates and regulators by steric hindrance. Our study provides a structural framework for understanding the mechanisms of ATM/Tel1 regulation as well as the development of new therapeutic agents. |
External links | Nat Commun / PubMed:27229179 / PubMed Central |
Methods | EM (single particle) |
Resolution | 8.7 Å |
Structure data | EMDB-6399: |
Source |
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