The Mad1-Sin3B interaction involves a novel helical fold

C.A.E.M. Spronk, M. Tessari, A.M. Kaan, J.F.A. Jansen, M. Vermeulen, H.G. Stunnenberg, G.W. Vuister

Research output: Contribution to journalArticleAcademicpeer-review

49 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1100-1104
Number of pages5
JournalNature Structural Biology
Volume7
Issue number12
DOIs
Publication statusPublished - Dec 2000
Externally publishedYes

Keywords

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Carrier Proteins
  • Cell Cycle Proteins
  • Conserved Sequence
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Nuclear Proteins
  • Phosphoproteins/chemistry
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Repressor Proteins/chemistry
  • Sequence Alignment
  • Solutions
  • Substrate Specificity
  • Transcription Factors

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