The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure

J Biol Chem. 1990 May 25;265(15):8573-82.


We have determined the domains of the mammalian high mobility group (HMG)I chromosomal proteins necessary and sufficient for binding to the narrow minor groove of stretches of A.T-rich DNA. Three highly conserved regions within each of the known HMG-I proteins is closely related to the consensus sequence T-P-K-R-P-R-G-R-P-K-K. A synthetic oligopeptide corresponding to this consensus "binding domain" (BD) sequence specifically binds to substrate DNA in a manner similar to the intact HMG-I proteins. Molecular Corey-Pauling-Koltun model building and computer simulations employing energy minimization programs to predict structure suggest that the consensus BD peptide has a secondary structure similar to the antitumor and antiviral drugs netropsin and distamycin and to the dye Hoechst 33258. In vitro these ligands, which also preferentially bind to A.T-rich DNA, have been demonstrated to effectively compete with both the BD peptide and the HMG-I proteins for DNA binding. The BD peptide also contains novel structural features such as a predicted Asx bend or "hook" at its amino-terminal end and laterally projecting cationic Arg/Lys side chains or "bristles" which may contribute to the binding properties of the HMG-I proteins. The predicted BD peptide structure, which we refer to as the "A.T-hook," represents a previously undescribed DNA-binding motif capable of binding to the minor groove of stretches of A.T base pairs.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Bisbenzimidazole / metabolism
  • Cattle
  • Computer Simulation
  • DNA / genetics
  • DNA / isolation & purification
  • DNA / metabolism*
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / isolation & purification
  • High Mobility Group Proteins / metabolism*
  • Humans
  • Interleukin-2 / genetics
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Protein Binding
  • Sequence Homology, Nucleic Acid
  • Thymine*


  • High Mobility Group Proteins
  • Interleukin-2
  • DNA
  • Adenine
  • Bisbenzimidazole
  • Thymine