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Article: Specific recognition of phosphorylated tail of H2AX by the tandem BRCT domains of MCPH1 revealed by complex structure

TitleSpecific recognition of phosphorylated tail of H2AX by the tandem BRCT domains of MCPH1 revealed by complex structure
Authors
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
Citation
Journal Of Structural Biology, 2012, v. 177 n. 2, p. 459-468 How to Cite?
Abstract
MCPH1 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.
Persistent Identifierhttp://hdl.handle.net/10722/144511
ISSN
2013 Impact Factor: 3.369
ISI Accession Number ID
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.

References

 

Author Affiliations
  1. The University of Hong Kong
  2. Hefei National Laboratory for Physical Sciences at Microscale
DC FieldValueLanguage
dc.contributor.authorShao, Zen_HK
dc.contributor.authorLi, Fen_HK
dc.contributor.authorSy, SMHen_HK
dc.contributor.authorYan, Wen_HK
dc.contributor.authorZhang, Zen_HK
dc.contributor.authorGong, Den_HK
dc.contributor.authorWen, Ben_HK
dc.contributor.authorHuen, MSYen_HK
dc.contributor.authorGong, Qen_HK
dc.contributor.authorWu, Jen_HK
dc.contributor.authorShi, Yen_HK
dc.date.accessioned2012-02-03T06:11:42Z-
dc.date.available2012-02-03T06:11:42Z-
dc.date.issued2012en_HK
dc.identifier.citationJournal Of Structural Biology, 2012, v. 177 n. 2, p. 459-468en_HK
dc.identifier.issn1047-8477en_HK
dc.identifier.urihttp://hdl.handle.net/10722/144511-
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.en_HK
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yjsbien_HK
dc.relation.ispartofJournal of Structural Biologyen_HK
dc.subjectγH2AXen_HK
dc.subjectBRCTen_HK
dc.subjectDNA damageen_HK
dc.subjectMCPH1en_HK
dc.subjectMDC1en_HK
dc.subjectSWI-SNFen_HK
dc.titleSpecific recognition of phosphorylated tail of H2AX by the tandem BRCT domains of MCPH1 revealed by complex structureen_HK
dc.typeArticleen_HK
dc.identifier.emailHuen, MSY:huen.michael@hku.hken_HK
dc.identifier.authorityHuen, MSY=rp01336en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jsb.2011.11.022en_HK
dc.identifier.pmid22154951-
dc.identifier.scopuseid_2-s2.0-84857033669en_HK
dc.identifier.hkuros198268en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84857033669&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume177en_HK
dc.identifier.issue2en_HK
dc.identifier.spage459en_HK
dc.identifier.epage468en_HK
dc.identifier.isiWOS:000300755400031-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridShao, Z=54414900500en_HK
dc.identifier.scopusauthoridLi, F=54414382900en_HK
dc.identifier.scopusauthoridSy, SMH=54901413200en_HK
dc.identifier.scopusauthoridYan, W=54415229400en_HK
dc.identifier.scopusauthoridZhang, Z=54682590100en_HK
dc.identifier.scopusauthoridGong, D=54681721800en_HK
dc.identifier.scopusauthoridWen, B=54682601100en_HK
dc.identifier.scopusauthoridHuen, MSY=23004751500en_HK
dc.identifier.scopusauthoridGong, Q=13006433900en_HK
dc.identifier.scopusauthoridWu, J=7409254824en_HK
dc.identifier.scopusauthoridShi, Y=7404964663en_HK
dc.identifier.citeulike10108671-

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