title: Multiple oligomeric states regulate the DNA binding of helix-loop-helix peptides.
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.
authors.affiliation: DuPont Merck Pharmaceutical Co., Wilmington, DE 19880-0328.
authors.forename: R
authors.initials: R
authors.lastname: Fairman
authors.forename: R K
authors.initials: RK
authors.lastname: Beran-Steed
authors.forename: S J
authors.initials: SJ
authors.lastname: Anthony-Cahill
authors.forename: J D
authors.initials: JD
authors.lastname: Lear
authors.forename: W F
authors.initials: WF
authors.lastname: Stafford
authors.forename: W F
authors.initials: WF
authors.lastname: DeGrado
authors.forename: P A
authors.initials: PA
authors.lastname: Benfield
authors.forename: S L
authors.initials: SL
authors.lastname: Brenner
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D051798:Inhibitor of Differentiation Protein 1; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D017570:MyoD Protein / Q000037:antagonists & inhibitors*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D012097:Repressor Proteins; D014157:Transcription Factors / Q000737:chemistry
chemical_list: D004268:DNA-Binding Proteins; D051798:Inhibitor of Differentiation Protein 1; D046911:Macromolecular Substances; D017570:MyoD Protein; D009838:Oligodeoxyribonucleotides; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA