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
2011 Impact Factor: 3.406
2011 SCImago Journal Rankings: 0.452
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 Field
Value
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
2011 Impact Factor: 3.406
2011 SCImago Journal Rankings: 0.452
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
Author Affiliations
  1. The University of Hong Kong
  2. University of Science and Technology of China