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Structure of the human dimeric ATM kinase
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-pa...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889239/ https://www.ncbi.nlm.nih.gov/pubmed/27097373 http://dx.doi.org/10.1080/15384101.2016.1158362 |
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author | Lau, Wilson C. Y. Li, Yinyin Liu, Zhe Gao, Yuanzhu Zhang, Qinfen Huen, Michael S. Y. |
author_facet | Lau, Wilson C. Y. Li, Yinyin Liu, Zhe Gao, Yuanzhu Zhang, Qinfen Huen, Michael S. Y. |
author_sort | Lau, Wilson C. Y. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4889239 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-48892392016-06-15 Structure of the human dimeric ATM kinase Lau, Wilson C. Y. Li, Yinyin Liu, Zhe Gao, Yuanzhu Zhang, Qinfen Huen, Michael S. Y. Cell Cycle Report 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. Taylor & Francis 2016-04-20 /pmc/articles/PMC4889239/ /pubmed/27097373 http://dx.doi.org/10.1080/15384101.2016.1158362 Text en © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. |
spellingShingle | Report Lau, Wilson C. Y. Li, Yinyin Liu, Zhe Gao, Yuanzhu Zhang, Qinfen Huen, Michael S. Y. Structure of the human dimeric ATM kinase |
title | Structure of the human dimeric ATM kinase |
title_full | Structure of the human dimeric ATM kinase |
title_fullStr | Structure of the human dimeric ATM kinase |
title_full_unstemmed | Structure of the human dimeric ATM kinase |
title_short | Structure of the human dimeric ATM kinase |
title_sort | structure of the human dimeric atm kinase |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889239/ https://www.ncbi.nlm.nih.gov/pubmed/27097373 http://dx.doi.org/10.1080/15384101.2016.1158362 |
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