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The Mad1–Sin3B interaction involves a novel helical fold

Nature Structural Biology volume 7, pages 1100–1104 (2000)Cite this article

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 α-helices of PAH2 form a hydrophobic cleft that accommodates an amphipathic Mad1 α-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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Figure 1: Sin3 architecture and Mad1 binding.
Figure 2: Solution structure of the PAH2–hMad1-SID complex.
Figure 3: Sequence conservation in PAH1 and PAH2 domains.
Figure 4: Structural differences between unbound PAH2 and PAH2 in complex with hMad1-SID.

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Acknowledgements

We thank J. Aelen for technical assistance and purification of the labeled proteins. We wish to thank the members of our Departments and J. Betz for suggestions and critical reading of the manuscript. We thank B. Eisenman for his generous gift of the mSin3 cDNAs, D. Reinberg for Sap30 antibody, and A. Gronenborn for the pGev2 construct. The research of C. Spronk and M. Vermeulen is financially supported by the Netherlands Organization for Scientific Research (NWO).

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  1. Department of Biophysical Chemistry, NSR Center, University of Nijmegen, The Netherlands

    Christian A. E. M. Spronk, Marco Tessari, Jacobus F. A. Jansen & Geerten W. Vuister

  2. Department of Molecular Biology, Institute of Cellular Signalling, University of Nijmegen, The Netherlands

    Anita M. Kaan, Michiel Vermeulen & Hendrik G. Stunnenberg

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  1. Christian A. E. M. Spronk
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Correspondence to Geerten W. Vuister.

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Spronk, C., Tessari, M., Kaan, A. et al. The Mad1–Sin3B interaction involves a novel helical fold. Nat Struct Mol Biol 7, 1100–1104 (2000). https://doi.org/10.1038/81944

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