PMID- 27097373 OWN - NLM STAT- MEDLINE DCOM- 20170106 LR - 20200930 IS - 1551-4005 (Electronic) IS - 1538-4101 (Print) IS - 1551-4005 (Linking) VI - 15 IP - 8 DP - 2016 TI - Structure of the human dimeric ATM kinase. PG - 1117-24 LID - 10.1080/15384101.2016.1158362 [doi] AB - 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. FAU - Lau, Wilson C Y AU - Lau WC AD - a School of Biomedical Sciences, The University of Hong Kong , Hong Kong. AD - b State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong , Hong Kong. FAU - Li, Yinyin AU - Li Y AD - c State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University , Guangzhou , China. FAU - Liu, Zhe AU - Liu Z AD - d Guangdong Provincial Center for Disease Control and Prevention , Guangzhou , China. FAU - Gao, Yuanzhu AU - Gao Y AD - c State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University , Guangzhou , China. FAU - Zhang, Qinfen AU - Zhang Q AD - c State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University , Guangzhou , China. FAU - Huen, Michael S Y AU - Huen MS AD - a School of Biomedical Sciences, The University of Hong Kong , Hong Kong. AD - b State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong , Hong Kong. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell Cycle JT - Cell cycle (Georgetown, Tex.) JID - 101137841 RN - 0 (Protein Subunits) RN - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins) SB - IM MH - Ataxia Telangiectasia Mutated Proteins/*chemistry/metabolism/ultrastructure MH - Humans MH - Image Processing, Computer-Assisted MH - Models, Molecular MH - Oxidation-Reduction MH - *Protein Multimerization MH - Protein Subunits/metabolism PMC - PMC4889239 OTO - NOTNLM OT - ATM kinase OT - DNA damage OT - DNA damage response OT - PIKK OT - ataxia telangiectasia OT - electron microscopy (EM) OT - post-translational modification (PTM) EDAT- 2016/04/21 06:00 MHDA- 2017/01/07 06:00 PMCR- 2016/04/20 CRDT- 2016/04/21 06:00 PHST- 2016/04/21 06:00 [entrez] PHST- 2016/04/21 06:00 [pubmed] PHST- 2017/01/07 06:00 [medline] PHST- 2016/04/20 00:00 [pmc-release] AID - 1158362 [pii] AID - 10.1080/15384101.2016.1158362 [doi] PST - ppublish SO - Cell Cycle. 2016;15(8):1117-24. doi: 10.1080/15384101.2016.1158362.