Solution structure of the interacting domains of the mad-sin3 complex: Implications for recruitment of a chromatin-modifying complex

Kurt Brubaker, Shaun M. Cowley, Kai Huang, Lenora Loo, Gregory S. Yochum, Donald E. Ayer, Robert N. Eisenman, Ishwar Radhakrishnan*

*Corresponding author for this work

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Gene-specific targeting of the Sin3 corepressor complex by DNA-bound repressors is an important mechanism of gene silencing in eukaryotes. The Sin3 corepressor specifically associates with a diverse group of transcriptional repressors, including members of the Mad family, that play crucial roles in development. The NMR structure of the complex formed bythe PAH2 domain of mammalian Sin3A with the transrepression domain (SID) of human Mad1 reveals that both domains undergo mutual folding transitions upon complex formation generating an unusual left-handed four-helix bundle structure and an amphipathic α helix, respectively. The SID helix is wedged within a deep hydrophobic pocket defined by two PAH2 helices. Structurefunction analyses of the Mad-Sin3 complex provide a basis for understanding the underlying mechanism(s) that lead to gene silencing.

Original languageEnglish (US)
Pages (from-to)655-665
Number of pages11
JournalCell
Volume103
Issue number4
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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