Total Chemical Synthesis of a Unique Transcription Factor-Related Protein: cMyc—Max

Lynne E. Canne, Adrian R. Ferré-D'Amaré, Stephen K. Burley, Stephen B.H. Kent

Research output: Contribution to journalArticle

173 Scopus citations

Abstract

cMyc and Max are proteins that regulate gene expression by associating to form noncovalent dimers that bind to specific regions of double-stranded DNA, thus activating or inhibiting mRNA transcription. Each of these transcription factor proteins contains an ~90 amino acid residue basic/helix—loop—helix/zipper (b/HLH/Z) domain responsible for formation of the protein dimers and for DNA binding. Noncovalent heterodimers of the cMyc and Max b/HLH/Z domains are believed to be functionally important in vivo but have not been accessible by conventional means (recDNA expression). Here we report the total chemical synthesis of novel covalently-linked dimers of the b/HLH/Z domains of these transcription factors by a modular strategy based on the convergent chemical ligation of several unprotected peptide segments. The resulting ~20 kDa synthetic proteins were purified to homogeneity and characterized by electrospray mass spectrometry. The synthetic covalent cMyc—Max heterodimer and the covalent Max homodimer control were shown to bind DNA specifically at the region involved in the regulation of mRNA transcription. Access to defined heterodimeric forms of the b/HLH/Z transcription factors will allow the structural and functional properties of these important protein regulators of gene expression to be studied.

Original languageEnglish (US)
Pages (from-to)2998-3007
Number of pages10
JournalJournal of the American Chemical Society
Volume117
Issue number11
DOIs
StatePublished - Mar 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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