Solution structure of the mSin3A PAH2-Pf1 SID1 complex: A Mad1/Mxd1-like interaction disrupted by MRG15 in the Rpd3S/Sin3S complex

Ganesan Senthil Kumar, Tao Xie, Yongbo Zhang, Ishwar Radhakrishnan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Histone deacetylation constitutes an important mechanism for silencing genes. The histone-deacetylase-associated mammalian Rpd3S/Sin3S corepressor complex plays key roles in repressing aberrant gene transcription from cryptic transcription initiation sites and in mitigating RNA polymerase II progression in intragenic regions of actively transcribed genes. The Sin3 corepressor functions as a molecular adaptor linking histone deacetylases on the one hand, with the chromatin targeting subunits Pf1 and MRG15 on the other. Pf1 also functions as an adaptor by interacting with MRG15 and engaging in multivalent interactions with Sin3 targeting among other domains the two N-terminal paired amphipathic helix (PAH) domains that serve as sites of interaction with sequence-specific DNA-binding transcription factors. Here, we structurally and functionally evaluate the interaction between the PAH2 domain of mSin3A and the Sin3 interaction domain 1 (SID1) motif of Pf1 and find the structural aspects to be reminiscent of the interaction between the Mad1/Mxd1 transcription factor and Sin3. Pf1 residues within a highly conserved sequence motif immediately C-terminal to SID1 appear not to be important for the interaction with Sin3 PAH2. Unexpectedly, the MRG15 subunit competes, rather than collaborates, with Sin3 for the Pf1 segment encompassing the two conserved motifs, implying competition between two subunits for another subunit of the same chromatin-modifying complex.

Original languageEnglish (US)
Pages (from-to)987-1000
Number of pages14
JournalJournal of Molecular Biology
Volume408
Issue number5
DOIs
StatePublished - May 20 2011

Keywords

  • 2D
  • 3D
  • COSY
  • HDAC
  • HSQC
  • ITC
  • MRG
  • NOE
  • NOE spectroscopy
  • NOESY
  • PAH
  • PDB
  • PHD
  • Protein Data Bank
  • SID
  • Sin3 interaction domain
  • TCEP
  • correlated spectroscopy
  • heteronuclear single quantum coherence
  • histone deacetylase
  • isothermal titration calorimetry
  • mortality factor on chromosome 4-related gene
  • nuclear Overhauser enhancement
  • paired amphipathic helix
  • plant homeodomain
  • three-dimensional
  • tris(2-carboxyethyl)phosphine hydrochloride
  • two-dimensional

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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