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TitleThe Nucleosome Remodeling and Deacetylase Complex Has an Asymmetric, Dynamic, and Modular Architecture.
Journal, issue, pagesCell Rep, Vol. 33, Issue 9, Page 108450, Year 2020
Publish dateDec 1, 2020
AuthorsJason K K Low / Ana P G Silva / Mehdi Sharifi Tabar / Mario Torrado / Sarah R Webb / Benjamin L Parker / Maryam Sana / Callum Smits / Jason W Schmidberger / Lou Brillault / Matthew J Jackman / David C Williams / Gerd A Blobel / Sandra B Hake / Nicholas E Shepherd / Michael J Landsberg / Joel P Mackay /
PubMed AbstractThe nucleosome remodeling and deacetylase (NuRD) complex is essential for metazoan development but has been refractory to biochemical analysis. We present an integrated analysis of the native ...The nucleosome remodeling and deacetylase (NuRD) complex is essential for metazoan development but has been refractory to biochemical analysis. We present an integrated analysis of the native mammalian NuRD complex, combining quantitative mass spectrometry, cross-linking, protein biochemistry, and electron microscopy to define the architecture of the complex. NuRD is built from a 2:2:4 (MTA, HDAC, and RBBP) deacetylase module and a 1:1:1 (MBD, GATAD2, and Chromodomain-Helicase-DNA-binding [CHD]) remodeling module, and the complex displays considerable structural dynamics. The enigmatic GATAD2 controls the asymmetry of the complex and directly recruits the CHD remodeler. The MTA-MBD interaction acts as a point of functional switching, with the transcriptional regulator PWWP2A competing with MBD for binding to the MTA-HDAC-RBBP subcomplex. Overall, our data address the long-running controversy over NuRD stoichiometry, provide imaging of the mammalian NuRD complex, and establish the biochemical mechanism by which PWWP2A can regulate NuRD composition.
External linksCell Rep / PubMed:33264611 / PubMed Central
MethodsEM (single particle)
Resolution14.0 - 29.0 Å
Structure data

EMDB-21382:
Negative stain EM map of an MTA-HDAC-MBD complex
Method: EM (single particle) / Resolution: 29.0 Å

EMDB-22895:
Low resolution map of the nucleosome remodelling and deacetylase complex from MEL cells.
Method: EM (single particle) / Resolution: 14.0 Å

EMDB-22904:
Low resolution map of the nucleosome deacetylase complex from murine erythroleukemia cells.
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-22905:
Map of the nucleosome deacetylase complex in a twisted conformation
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-22906:
The untwisted conformation of the nucleosome deacetylase complex
Method: EM (single particle) / Resolution: 20.0 Å

Source
  • Mus musculus (house mouse)
  • Homo sapiens (human)

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