Molecular characterization of helix-loop-helix peptides

Science. 1992 Feb 21;255(5047):979-83. doi: 10.1126/science.1312255.


A class of regulators of eukaryotic gene expression contains a conserved amino acid sequence responsible for protein oligomerization and binding to DNA. This structure consists of an arginine- and lysine-rich basic region followed by a helix-loop-helix motif, which together mediate specific binding to DNA. Peptides were prepared that span this motif in the MyoD protein; in solution, they formed alpha-helical dimers and tetramers. They bound to DNA as dimers and their alpha-helical content increased on binding. Parallel and antiparallel four-helix models of the DNA-bound dimer were constructed. Peptides containing disulfide bonds were engineered to test the correctness of the two models. A disulfide that is compatible with the parallel model promotes specific interaction with DNA, whereas a disulfide compatible with the antiparallel model abolishes specific binding. Electron paramagnetic resonance (EPR) measurements of nitroxide-labeled peptides provided intersubunit distance measurements that also supported the parallel model.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Circular Dichroism
  • DNA-Binding Proteins / chemistry*
  • Disulfides
  • Electron Spin Resonance Spectroscopy
  • Enhancer Elements, Genetic
  • Gene Expression Regulation
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Regulatory Sequences, Nucleic Acid
  • Sequence Alignment
  • Transcription Factors / chemistry*


  • DNA-Binding Proteins
  • Disulfides
  • Transcription Factors