Coupled Unfolding and Dimerization by the PAH2 Domain of the Mammalian Sin3A Corepressor

Yongbo Zhang, Zhipeng Zhang, Borries Demeler, Ishwar Radhakrishnan

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Coregulator recruitment by sequence-specific DNA binding transcription factors constitutes an important step in many eukaryotic transcription regulatory pathways. The Sin3 corepressor is an evolutionarily conserved protein and a key component of a large histone deacetylase-associated corepressor complex. The Sin3 corepressor contains four imperfect repeats of a domain called PAH (paired amphipathic helix) that serve as docking sites for a variety of sequence-specific DNA binding factors and coregulators. At least two closely related Sin3 proteins designated Sin3A and Sin3B have been described in higher organisms and although functional differences between these paralogs are only beginning to be appreciated, differences at the structural level are poorly understood. Here we analyze the conformational properties of the apo form of the mammalian Sin3A (mSin3A) PAH2 domain. At low micromolar concentrations, the domain is predominantly monomeric and folded in a conformation similar to those found in complexes with the Mad1 and HBP1 repressors. Unexpectedly, at higher concentrations, the domain dimerizes with concomitant population of a partially unfolded conformer. These findings are in contrast to those reported for the mSin3B PAH2 domain and may have implications for the manner in which these paralogous domains interact with their targets.

Original languageEnglish
Pages (from-to)7-14
Number of pages8
JournalJournal of Molecular Biology
Issue number1
StatePublished - Jun 30 2006


  • PAH2 domain
  • Sin3 corepressor
  • protein dimerization
  • protein structure
  • protein unfolding


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