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Updated: Mar 22, 2026
11:27
A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
Published on: November 2, 2018
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Structure of the human dimeric ATM kinase
Wilson C Y Lau1,2, Yinyin Li3, Zhe Liu4
1a School of Biomedical Sciences, The University of Hong Kong , Hong Kong.
Cell Cycle (Georgetown, Tex.)
|April 21, 2016
Summary
The ataxia-telangiectasia mutated (ATM) protein kinase, crucial for DNA damage response, remains inactive as a dimer. Its structure reveals buried active sites, explaining how ATM is inhibited in its resting state.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- DNA double-strand breaks (DSBs) trigger cellular responses.
- The serine/threonine protein kinase ataxia-telangiectasia mutated (ATM) is central to DNA damage signal transduction.
- ATM activation involves autophosphorylation and dissociation of inactive dimers into active monomers.
Purpose of the Study:
- To determine the structure of dimeric ATM in its resting state using single-particle electron microscopy (EM).
- To understand the mechanism of ATM inhibition based on its structural organization.
Main Methods:
- Single-particle electron microscopy (EM) to visualize dimeric ATM.
- Integration of crystal structure data of N-terminal truncated mammalian target of rapamycin (mTOR) to localize ATM domains.
Main Results:
- The structure of dimeric ATM in its resting state was determined.
- The EM map allowed localization of N- and C-terminal regions of ATM by accommodating the mTOR crystal structure.
- The dimeric ATM structure revealed that active sites are buried, restricting substrate access.
Conclusions:
- The unanticipated domain organization of dimeric ATM explains its inhibited state.
- This structural insight provides a foundation for understanding ATM regulation in DNA damage response.
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