A Flexible Extension of the Drosophila Ultrabithorax Homeodomain Defines a Novel Hox/PBC Interaction Mode

• Published in: Structure (London) 2015-02, Vol.23 (2), p.270-279
• Main Authors: Foos, Nicolas, Maurel-Zaffran, Corinne, Maté, María Jesús, Vincentelli, Renaud, Hainaut, Matthieu, Berenger, Hélène, Pradel, Jacques, Saurin, Andrew J., Ortiz-Lombardía, Miguel, Graba, Yacine
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Biochemistry, Molecular Biology; Crystallization; DNA - metabolism; Drosophila - chemistry; Drosophila Proteins - chemistry; Drosophila Proteins - metabolism; Electrophoretic Mobility Shift Assay; Homeodomain Proteins - chemistry; Homeodomain Proteins - metabolism; Life Sciences; Macromolecular Substances - metabolism; Models, Molecular; Molecular Probes - genetics; Molecular Sequence Data; Protein Folding; Protein Structure, Tertiary; Quantitative Methods; Structural Biology; Transcription Factors - chemistry; Transcription Factors - metabolism
• ISSN: 0969-2126; 1878-4186
• 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. [Display omitted] •The Ultrabithorax UbdA domain extends the HD recognition helix•The extension of the HD recognition helix provides a novel interface toward Exd•Structure-based UbdA-mediated Exd contacts are important for Exd-dependent functions Diverse functions of Hox/PBC complexes likely involve multiple interaction modes. Foos et al. structurally characterize a novel Hox/PBC interaction mode, which defines a new molecular facet to the Hox/PBC complex assembly.