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

Derek E. Piper, Adrian H. Batchelor, Ching-Pin Chang, Michael L. Cleary, Cynthia Wolberger

Research output: Contribution to journalArticle

261 Citations (Scopus)

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 Å 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 fie 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 α 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.

Original languageEnglish (US)
Pages (from-to)587-597
Number of pages11
JournalCell
Volume96
Issue number4
StatePublished - Feb 19 1999
Externally publishedYes

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DNA
Homeodomain Proteins
Proteins
Vertebrates
Modulation
Amino Acids

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Piper, D. E., Batchelor, A. H., Chang, C-P., Cleary, M. L., & Wolberger, C. (1999). Structure of a HoxB1-Pbx1 heterodimer bound to DNA: Role of the hexapeptide and a fourth homeodomain helix in complex formation. Cell, 96(4), 587-597.

Structure of a HoxB1-Pbx1 heterodimer bound to DNA : Role of the hexapeptide and a fourth homeodomain helix in complex formation. / Piper, Derek E.; Batchelor, Adrian H.; Chang, Ching-Pin; Cleary, Michael L.; Wolberger, Cynthia.

In: Cell, Vol. 96, No. 4, 19.02.1999, p. 587-597.

Research output: Contribution to journalArticle

Piper, DE, Batchelor, AH, Chang, C-P, Cleary, ML & Wolberger, C 1999, 'Structure of a HoxB1-Pbx1 heterodimer bound to DNA: Role of the hexapeptide and a fourth homeodomain helix in complex formation', Cell, vol. 96, no. 4, pp. 587-597.
Piper DE, Batchelor AH, Chang C-P, Cleary ML, Wolberger C. 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):587-597.
Piper, Derek E. ; Batchelor, Adrian H. ; Chang, Ching-Pin ; Cleary, Michael L. ; Wolberger, Cynthia. / Structure of a HoxB1-Pbx1 heterodimer bound to DNA : Role of the hexapeptide and a fourth homeodomain helix in complex formation. In: Cell. 1999 ; Vol. 96, No. 4. pp. 587-597.
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