title: Solution NMR Studies of an Alternative Mode of Sin3 Engagement by the Sds3 Subunit in the Histone Deacetylase-Associated Sin3L/Rpd3L Corepressor Complex.
abstract: The Sds3 transcriptional corepressor facilitates the assembly of the 1- to 2-MDa histone deacetylase-associated Sin3L/Rpd3L complex by providing a crucial homodimerization activity. Sds3 engages the scaffolding protein Sin3A, via a bipartite motif within the Sin3 interaction domain (SID) comprising a helix and an extended segment. Here, we show that the SID samples two discrete, substantially populated conformations with lifetimes in the tens of milliseconds range. The two conformations differ via a translation of the main chain and the corresponding side chains in the 5- to 7-Å range. Given the close proximity of the SID to other functional motifs in Sds3 at the sequence level, the conformational exchange has the potential to regulate these activities.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Michael David
authors.initials: MD
authors.lastname: Clark
authors.affiliation: Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA. Electronic address: i-radhakrishnan@northwestern.edu.
authors.forename: Ishwar
authors.initials: I
authors.lastname: Radhakrishnan
mesh_terms: D000595:Amino Acid Sequence; D056284:Histone Deacetylase 1 / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D021122:Protein Subunits; D012097:Repressor Proteins / Q000737:chemistry*; D056264:Sin3 Histone Deacetylase and Corepressor Complex / Q000737:chemistry*; D012996:Solutions
chemical_list: D021122:Protein Subunits; D012097:Repressor Proteins; C576731:SUDS3 protein, human; D012996:Solutions; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D056264:Sin3 Histone Deacetylase and Corepressor Complex
keywords: NMR spectroscopy; conformational exchange; conformational heterogeneity; multiple binding modes; protein–protein interaction