Insight into the Architecture of the NuRD Complex: Structure of the RbAp48-MTA1 Subcomplex
- Creators
- Alqarni, Saad S. M.
- Murthy, Andal
- Zhang, Wei
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Przewloka, Marcin R.
- Silva, Ana P. G.
- Watson, Aleksandra A.
- Lejon, Sara
- Pei, Xue Y.
- Smits, Arne H.
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Kloet, Susan L.
- Wang, Hongxin
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Shepherd, Nicholas E.
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Stokes, Philippa H.
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Blobel, Gerd A.
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Vermeulen, Michiel
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Glover, David M.
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Mackay, Joel P.
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Laue, Ernest D.
Abstract
The nucleosome remodeling and deacetylase (NuRD) complex is a widely conserved transcriptional co-regulator that harbors both nucleosome remodeling and histone deacetylase activities. It plays a critical role in the early stages of ES cell differentiation and the reprogramming of somatic to induced pluripotent stem cells. Abnormalities in several NuRD proteins are associated with cancer and aging. We have investigated the architecture of NuRD by determining the structure of a subcomplex comprising RbAp48 and MTA1. Surprisingly, RbAp48 recognizes MTA1 using the same site that it uses to bind histone H4, showing that assembly into NuRD modulates RbAp46/48 interactions with histones. Taken together with other results, our data show that the MTA proteins act as scaffolds for NuRD complex assembly. We further show that the RbAp48-MTA1 interaction is essential for the in vivo integration of RbAp46/48 into the NuRD complex.
Additional Information
© 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Creative Commons Attribution Unported License applies to Author Choice Articles. Received February 18, 2014. Revision received May 30, 2014. We thank Janusz Debski and Michal Dadlez (Institute of Biochemistry and Biophysics, Polish Academy of Sciences) for the mass spectrometry analysis of protein samples purified from D. melanogaster cells. We also thank the Drosophila Genomics Resource Center, which is supported by the National Institutes of Health Grant OD010949-10, for Drosophila cDNA clones. We are grateful to Prof. Ben F. Luisi for help with X-ray data collection. We also thank the European Commission for support through the 4DCellFate project (EC FP7 CP 277899). Recipient of Wellcome Trust Fellowship 092441/Z/10/Z. Supported by a Wellcome Trust program grant awarded to Professor Ben F. Luisi (076846/Z/05/A). An Australian Research Council DECRA (Discovery Early Career Researcher Award) Fellow. This work was supported by program grants from Cancer Research UK and the Medical Research Council (C3/A11431 and G1001696, respectively; to D. M. G.), National Health and Medical Research Council Grant 1012161 (to J. P. M.), and the Wellcome Trust (082010/Z/07/Z; to E. D. L.). The atomic coordinates and structure factors (codes 4PBY, 4PBZ, and 4PC0) have been deposited in the Protein Data Bank (http://wwpdb.org/).Attached Files
Published - J._Biol._Chem.-2014-Alqarni-21844-55.pdf
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Additional details
- PMCID
- PMC4139204
- Eprint ID
- 104858
- Resolver ID
- CaltechAUTHORS:20200807-170352671
- OD010949-10
- NIH
- 277899
- European Research Council (ERC)
- 092441/Z/10/Z
- Wellcome Trust
- 076846/Z/05/A
- Wellcome Trust
- Australian Research Council
- C3/A11431
- Cancer Research UK
- G1001696
- Medical Research Council (UK)
- 1012161
- National Health and Medical Research Council (NHMRC)
- 082010/Z/07/Z
- Wellcome Trust
- Created
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2020-08-19Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field