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Article: Specific recognition of phosphorylated tail of H2AX by the tandem BRCT domains of MCPH1 revealed by complex structure
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TitleSpecific recognition of phosphorylated tail of H2AX by the tandem BRCT domains of MCPH1 revealed by complex structure
 
AuthorsShao, Z2
Li, F2
Sy, SMH1
Yan, W2
Zhang, Z2
Gong, D2
Wen, B2
Huen, MSY1
Gong, Q2
Wu, J2
Shi, Y2
 
KeywordsγH2AX
BRCT
DNA damage
MCPH1
MDC1
SWI-SNF
 
Issue Date2012
 
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yjsbi
 
CitationJournal Of Structural Biology, 2012, v. 177 n. 2, p. 459-468 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.jsb.2011.11.022
 
AbstractMCPH1 is especially important for linking chromatin remodeling to DNA damage response. It contains three BRCT (BRCA1-carboxyl terminal) domains. The N-terminal region directly binds with chromatin remodeling complex SWI-SNF, and the C-terminal BRCT2-BRCT3 domains (tandem BRCT domains) are involved in cellular DNA damage response. The MCPH1 gene associates with evolution of brain size, and its variation can cause primary microcephaly. In this study we solve the crystal structures of MCPH1 natural variant (A761) C-terminal tandem BRCT domains alone as well as in complex with γH2AX tail. Compared with other structures of tandem BRCT domains, the most significant differences lie in phosphopeptide binding pocket. Additionally, fluorescence polarization assays demonstrate that MCPH1 tandem BRCT domains show a binding selectivity on pSer +3 and prefer to bind phosphopeptide with free COOH-terminus. Taken together, our research provides new structural insights into BRCT-phosphopeptide recognition mechanism. © 2011 Elsevier Inc.
 
ISSN1047-8477
2012 Impact Factor: 3.361
2012 SCImago Journal Rankings: 1.846
 
DOIhttp://dx.doi.org/10.1016/j.jsb.2011.11.022
 
ISI Accession Number IDWOS:000300755400031
Funding AgencyGrant Number
National Basic Research Program of China (973 Program)2011CB966302
2011CB911104
Chinese National Natural Science Foundation30830031
Chinese Academy of Sciences
Fundamental Research Funds for the Central Universities
Funding Information:

We gratefully thank Dr. Jianye Zang and Mr. Minhao Wu for their kindly help in the data collection process at Shanghai Synchrotron Radiation Facility. We thank Dr. Yuxing Chen, Yongliang Jiang, Fangming Wu, Yu Qiu, Bo Wu, Lei Liu, Weiwei Wang, Xinxin Li, Zhenwei Song, and Yang Zhou for their helpful discussions about the experiments and manuscript. This work was financially supported by National Basic Research Program of China (973 Program) (Grants 2011CB966302 and 2011CB911104), the Chinese National Natural Science Foundation (Grant 30830031), and the "Outstanding technical talent" project of the Chinese Academy of Sciences. Z.Z is grateful to support by the Fundamental Research Funds for the Central Universities. Single crystal X-ray diffraction data were collected at Shanghai Synchrotron Radiation Facility (SSRF) using beamline BL17U.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorShao, Z
 
dc.contributor.authorLi, F
 
dc.contributor.authorSy, SMH
 
dc.contributor.authorYan, W
 
dc.contributor.authorZhang, Z
 
dc.contributor.authorGong, D
 
dc.contributor.authorWen, B
 
dc.contributor.authorHuen, MSY
 
dc.contributor.authorGong, Q
 
dc.contributor.authorWu, J
 
dc.contributor.authorShi, Y
 
dc.date.accessioned2012-02-03T06:11:42Z
 
dc.date.available2012-02-03T06:11:42Z
 
dc.date.issued2012
 
dc.description.abstractMCPH1 is especially important for linking chromatin remodeling to DNA damage response. It contains three BRCT (BRCA1-carboxyl terminal) domains. The N-terminal region directly binds with chromatin remodeling complex SWI-SNF, and the C-terminal BRCT2-BRCT3 domains (tandem BRCT domains) are involved in cellular DNA damage response. The MCPH1 gene associates with evolution of brain size, and its variation can cause primary microcephaly. In this study we solve the crystal structures of MCPH1 natural variant (A761) C-terminal tandem BRCT domains alone as well as in complex with γH2AX tail. Compared with other structures of tandem BRCT domains, the most significant differences lie in phosphopeptide binding pocket. Additionally, fluorescence polarization assays demonstrate that MCPH1 tandem BRCT domains show a binding selectivity on pSer +3 and prefer to bind phosphopeptide with free COOH-terminus. Taken together, our research provides new structural insights into BRCT-phosphopeptide recognition mechanism. © 2011 Elsevier Inc.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Structural Biology, 2012, v. 177 n. 2, p. 459-468 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.jsb.2011.11.022
 
dc.identifier.citeulike10108671
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.jsb.2011.11.022
 
dc.identifier.epage468
 
dc.identifier.hkuros198268
 
dc.identifier.isiWOS:000300755400031
Funding AgencyGrant Number
National Basic Research Program of China (973 Program)2011CB966302
2011CB911104
Chinese National Natural Science Foundation30830031
Chinese Academy of Sciences
Fundamental Research Funds for the Central Universities
Funding Information:

We gratefully thank Dr. Jianye Zang and Mr. Minhao Wu for their kindly help in the data collection process at Shanghai Synchrotron Radiation Facility. We thank Dr. Yuxing Chen, Yongliang Jiang, Fangming Wu, Yu Qiu, Bo Wu, Lei Liu, Weiwei Wang, Xinxin Li, Zhenwei Song, and Yang Zhou for their helpful discussions about the experiments and manuscript. This work was financially supported by National Basic Research Program of China (973 Program) (Grants 2011CB966302 and 2011CB911104), the Chinese National Natural Science Foundation (Grant 30830031), and the "Outstanding technical talent" project of the Chinese Academy of Sciences. Z.Z is grateful to support by the Fundamental Research Funds for the Central Universities. Single crystal X-ray diffraction data were collected at Shanghai Synchrotron Radiation Facility (SSRF) using beamline BL17U.

 
dc.identifier.issn1047-8477
2012 Impact Factor: 3.361
2012 SCImago Journal Rankings: 1.846
 
dc.identifier.issue2
 
dc.identifier.pmid22154951
 
dc.identifier.scopuseid_2-s2.0-84857033669
 
dc.identifier.spage459
 
dc.identifier.urihttp://hdl.handle.net/10722/144511
 
dc.identifier.volume177
 
dc.languageeng
 
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yjsbi
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Structural Biology
 
dc.relation.referencesReferences in Scopus
 
dc.subjectγH2AX
 
dc.subjectBRCT
 
dc.subjectDNA damage
 
dc.subjectMCPH1
 
dc.subjectMDC1
 
dc.subjectSWI-SNF
 
dc.titleSpecific recognition of phosphorylated tail of H2AX by the tandem BRCT domains of MCPH1 revealed by complex structure
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. Hefei National Laboratory for Physical Sciences at Microscale