Structure of the human dimeric ATM kinase

Cell Cycle. 2016;15(8):1117-24. doi: 10.1080/15384101.2016.1158362.


DNA-double strand breaks activate the serine/threonine protein kinase ataxia-telangiectasia mutated (ATM) to initiate DNA damage signal transduction. This activation process involves autophosphorylation and dissociation of inert ATM dimers into monomers that are catalytically active. Using single-particle electron microscopy (EM), we determined the structure of dimeric ATM in its resting state. The EM map could accommodate the crystal structure of the N-terminal truncated mammalian target of rapamycin (mTOR), a closely related enzyme of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family, allowing for the localization of the N- and the C-terminal regions of ATM. In the dimeric structure, the actives sites are buried, restricting the access of the substrates to these sites. The unanticipated domain organization of ATM provides a basis for understanding its mechanism of inhibition.

Keywords: ATM kinase; DNA damage; DNA damage response; PIKK; ataxia telangiectasia; electron microscopy (EM); post-translational modification (PTM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / chemistry*
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Ataxia Telangiectasia Mutated Proteins / ultrastructure
  • Humans
  • Image Processing, Computer-Assisted
  • Models, Molecular
  • Oxidation-Reduction
  • Protein Multimerization*
  • Protein Subunits / metabolism


  • Protein Subunits
  • Ataxia Telangiectasia Mutated Proteins