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Structure of the intact ATM/Tel1 kinase

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  • Xuejuan Wang

    (Key Laboratory of Agricultural and Environmental Microbiology, Ministry of Agriculture, College of Life Sciences, Nanjing Agricultural University
    School of Life Sciences, University of Science and Technology of China)

  • Huanyu Chu

    (School of Life Sciences, University of Science and Technology of China)

  • Mengjuan Lv

    (School of Life Sciences, University of Science and Technology of China)

  • Zhihui Zhang

    (School of Life Sciences, University of Science and Technology of China)

  • Shuwan Qiu

    (School of Life Sciences, University of Science and Technology of China)

  • Haiyan Liu

    (School of Life Sciences, University of Science and Technology of China)

  • Xuetong Shen

    (University of Texas M.D. Anderson Cancer Center)

  • Weiwu Wang

    (Key Laboratory of Agricultural and Environmental Microbiology, Ministry of Agriculture, College of Life Sciences, Nanjing Agricultural University)

  • Gang Cai

    (School of Life Sciences, University of Science and Technology of China
    Hefei National Laboratory for Physical Sciences at the Microscale, Center for Integrative Imaging
    Center for Biomedical Engineering, University of Science and Technology of China)

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 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.

Suggested Citation

  • Xuejuan Wang & Huanyu Chu & Mengjuan Lv & Zhihui Zhang & Shuwan Qiu & Haiyan Liu & Xuetong Shen & Weiwu Wang & Gang Cai, 2016. "Structure of the intact ATM/Tel1 kinase," Nature Communications, Nature, vol. 7(1), pages 1-8, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11655
    DOI: 10.1038/ncomms11655
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