A flexible extension of the Drosophila ultrabithorax homeodomain defines a novel Hox/PBC interaction mode

Structure. 2015 Feb 3;23(2):270-9. doi: 10.1016/j.str.2014.12.011.


The patterning function of Hox proteins relies on assembling protein complexes with PBC proteins, which often involves a protein motif found in most Hox proteins, the so-called Hexapeptide (HX). Hox/PBC complexes likely gained functional diversity by acquiring additional modes of interaction. Here, we structurally characterize the first HX alternative interaction mode based on the paralogue-specific UbdA motif and further functionally validate structure-based predictions. The UbdA motif folds as a flexible extension of the homeodomain recognition helix and defines Hox/PBC contacts that occur, compared with those mediated by the HX motif, on the opposing side of the DNA double helix. This provides a new molecular facet to Hox/PBC complex assembly and suggests possible mechanisms for the diversification of Hox protein function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crystallization
  • DNA / metabolism*
  • Drosophila / chemistry*
  • Drosophila Proteins / chemistry*
  • Drosophila Proteins / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Homeodomain Proteins / chemistry*
  • Homeodomain Proteins / metabolism*
  • Macromolecular Substances / metabolism*
  • Models, Molecular*
  • Molecular Probes / genetics
  • Molecular Sequence Data
  • Protein Folding
  • Protein Structure, Tertiary
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism*


  • Drosophila Proteins
  • Homeodomain Proteins
  • Macromolecular Substances
  • Molecular Probes
  • Transcription Factors
  • Ubx protein, Drosophila
  • exd protein, Drosophila
  • DNA

Associated data

  • PDB/4CYC
  • PDB/4UUS
  • PDB/4UUT