Multiple oligomeric states regulate the DNA binding of helix-loop-helix peptides

Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10429-33. doi: 10.1073/pnas.90.22.10429.

Abstract

To study the protein-protein interactions that allow Id, a negative regulator of cell differentiation, to inhibit the DNA-binding activities of MyoD and E47, we have synthesized peptides corresponding to the helix-loop-helix domains of MyoD, E47, and Id. We show that Id preferentially inhibits the sequence-specific DNA-binding activity of MyoD, a muscle-specific protein, as compared to E47, a more ubiquitous protein. The Id helix-loop-helix domain itself forms stable tetramers, and its inhibitory activity arises from the formation of a heterotetrameric structure with MyoD. The formation of this higher order complex provides a general mechanism by which inhibitory proteins can generate sufficient interaction free energy to overcome the large DNA-binding free energy of dimeric DNA-binding proteins.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation*
  • Helix-Loop-Helix Motifs
  • Inhibitor of Differentiation Protein 1
  • Macromolecular Substances
  • Molecular Sequence Data
  • MyoD Protein / antagonists & inhibitors*
  • Oligodeoxyribonucleotides / chemistry
  • Protein Binding
  • Protein Conformation
  • Repressor Proteins*
  • Transcription Factors / chemistry

Substances

  • DNA-Binding Proteins
  • Inhibitor of Differentiation Protein 1
  • Macromolecular Substances
  • MyoD Protein
  • Oligodeoxyribonucleotides
  • Repressor Proteins
  • Transcription Factors
  • DNA