Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the hexapeptide and a fourth homeodomain helix in complex formation

Cell. 1999 Feb 19;96(4):587-97. doi: 10.1016/s0092-8674(00)80662-5.

Abstract

Hox homeodomain proteins are developmental regulators that determine body plan in a variety of organisms. A majority of the vertebrate Hox proteins bind DNA as heterodimers with the Pbx1 homeodomain protein. We report here the 2.35 A structure of a ternary complex containing a human HoxB1-Pbx1 heterodimer bound to DNA. Heterodimer contacts are mediated by the hexapeptide of HoxB1, which binds in a pocket in the Pbx1 protein formed in part by a three-amino acid insertion in the Pbx1 homeodomain. The Pbx1 DNA-binding domain is larger than the canonical homeodomain, containing an additional alpha helix that appears to contribute to binding of the HoxB1 hexapeptide and to stable binding of Pbx1 to DNA. The structure suggests a model for modulation of Hox DNA binding activity by Pbx1 and related proteins.

Publication types

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

MeSH terms

  • DNA / chemistry
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics*
  • Dimerization
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / chemistry*
  • Homeodomain Proteins / genetics*
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments / genetics
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins / genetics*
  • Sequence Homology, Amino Acid

Substances

  • DNA-Binding Proteins
  • HOXB1 homeodomain protein
  • Homeodomain Proteins
  • Peptide Fragments
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Proto-Oncogene Proteins
  • pbx1 protein, human
  • DNA

Associated data

  • PDB/1B72