2N2H

Solution structure of Sds3 in complex with Sin3A

Summary for 2N2H

• Entry DOI: 10.2210/pdb2n2h/pdb
• NMR Information: BMRB: 25599
• Descriptor: Sin3 histone deacetylase corepressor complex component SDS3, Paired amphipathic helix protein Sin3a (2 entities in total)
• Functional Keywords: transcription repression, corepressor complex, histone deacetylase complex, transcription, protein binding
• Biological source: Mus musculus (mouse); More
• Cellular location: Nucleus : Q8BR65 Q60520
• Total number of polymer chains: 2
• Total formula weight: 17824.35

Authors

Clark, M.,Radhakrishnan, I. (deposition date: 2015-05-08, release date: 2015-07-15, Last modification date: 2024-05-15)

Primary citation

Clark, M.D.,Marcum, R.,Graveline, R.,Chan, C.W.,Xie, T.,Chen, Z.,Ding, Y.,Zhang, Y.,Mondragon, A.,David, G.,Radhakrishnan, I.
Structural insights into the assembly of the histone deacetylase-associated Sin3L/Rpd3L corepressor complex.
Proc.Natl.Acad.Sci.USA, 112:E3669-E3678, 2015

PubMed Abstract: Acetylation is correlated with chromatin decondensation and transcriptional activation, but its regulation by histone deacetylase (HDAC)-bearing corepressor complexes is poorly understood. Here, we describe the mechanism of assembly of the mammalian Sin3L/Rpd3L complex facilitated by Sds3, a conserved subunit deemed critical for proper assembly. Sds3 engages a globular, helical region of the HDAC interaction domain (HID) of the scaffolding protein Sin3A through a bipartite motif comprising a helix and an adjacent extended segment. Sds3 dimerizes through not only one of the predicted coiled-coil motifs but also, the segment preceding it, forming an ∼ 150-Å-long antiparallel dimer. Contrary to previous findings in yeast, Sin3A rather than Sds3 functions in recruiting HDAC1 into the complex by engaging the latter through a highly conserved segment adjacent to the helical HID subdomain. In the resulting model for the ternary complex, the two copies of the HDACs are situated distally and dynamically because of a natively unstructured linker connecting the dimerization domain and the Sin3A interaction domain of Sds3; these features contrast with the static organization described previously for the NuRD (nucleosome remodeling and deacetylase) complex. The Sds3 linker features several conserved basic residues that could potentially maintain the complex on chromatin by nonspecific interactions with DNA after initial recruitment by sequence-specific DNA-binding repressors.

PubMed: 26124119
DOI: 10.1073/pnas.1504021112

Experimental method

SOLUTION NMR