2L2L

Solution structure of the coiled-coil complex between MBD2 and p66alpha

Summary for 2L2L

• Entry DOI: 10.2210/pdb2l2l/pdb
• NMR Information: BMRB: 17138
• Descriptor: Transcriptional repressor p66-alpha, Methyl-CpG-binding domain protein 2 (2 entities in total)
• Functional Keywords: dna methylation, coiled-coil, nurd, mbd2, p66alpha, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 9297.80

Authors

Williams Jr., D.C.,Scarsdale Jr., N. (deposition date: 2010-08-20, release date: 2011-05-04, Last modification date: 2024-05-01)

Primary citation

Gnanapragasam, M.N.,Scarsdale, J.N.,Amaya, M.L.,Webb, H.D.,Desai, M.A.,Walavalkar, N.M.,Wang, S.Z.,Zu Zhu, S.,Ginder, G.D.,Williams, D.C.
p66Alpha-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex.
Proc.Natl.Acad.Sci.USA, 108:7487-7492, 2011

PubMed Abstract: Nucleosome remodeling complexes comprise several large families of chromatin modifiers that integrate multiple epigenetic control signals to play key roles in cell type-specific transcription regulation. We previously isolated a methyl-binding domain protein 2 (MBD2)-containing nucleosome remodeling and deacetylation (NuRD) complex from primary erythroid cells and showed that MBD2 contributes to DNA methylation-dependent embryonic and fetal β-type globin gene silencing during development in vivo. Here we present structural and biophysical details of the coiled-coil interaction between MBD2 and p66α, a critical component of the MBD2-NuRD complex. We show that enforced expression of the isolated p66α coiled-coil domain relieves MBD2-mediated globin gene silencing and that the expressed peptide interacts only with a subset of components of the MBD2-NuRD complex that does not include native p66α or Mi-2. These results demonstrate the central importance of the coiled-coil interaction and suggest that MBD2-dependent DNA methylation-driven gene silencing can be disrupted by selectively targeting this coiled-coil complex.

PubMed: 21490301
DOI: 10.1073/pnas.1015341108

Experimental method

SOLUTION NMR