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The Mad1-Sin3B interaction involves a novel helical fold.

C A Spronk·M Tessari·A M Kaan·J F Jansen·M Vermeulen·H G Stunnenberg·G W Vuister
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Abstract

Sin3A or Sin3B are components of a corepressor complex that mediates repression by transcription factors such as the helix-loop-helix proteins Mad and Mxi. Members of the Mad/Mxi family of repressors play important roles in the transition between proliferation and differentiation by down-regulating the expression of genes that are activated by the proto-oncogene product Myc. Here, we report the solution structure of the second paired amphipathic helix (PAH) domain (PAH2) of Sin3B in complex with a peptide comprising the N-terminal region of Mad1. This complex exhibits a novel interaction fold for which we propose the name 'wedged helical bundle'. Four alpha-helices of PAH2 form a hydrophobic cleft that accommodates an amphipathic Mad1 alpha-helix. Our data further show that, upon binding Mad1, secondary structure elements of PAH2 are stabilized. The PAH2-Mad1 structure provides the basis for determining the principles of protein interaction and selectivity involving PAH domains.

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Amino Acid SequenceAnimalsBinding SitesCarrier ProteinsCell Cycle ProteinsConserved SequenceHumansMiceModels, MolecularMolecular Sequence DataNuclear Magnetic Resonance, BiomolecularNuclear ProteinsPhosphoproteinsProtein BindingProtein Structure, SecondaryProtein Structure, TertiaryProto-Oncogene MasRepressor ProteinsSequence AlignmentSolutionsSubstrate SpecificityTranscription FactorsJournal ArticleResearch Support, Non-U.S. Gov't

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C A Spronk, M Tessari, A M Kaan, J F Jansen, M Vermeulen, H G Stunnenberg, G W Vuister. 2000. The Mad1-Sin3B interaction involves a novel helical fold.. https://doi.org/10.1038/81944

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