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

By D. Piper, A. Batchelor, C. Chang, M. Cleary, C. Wolberger. 1999

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.

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Citations in the corpus

Structure of HoxA9 and Pbx1 bound to DNA: Hox hexapeptide and DNA recognition anterior to posterior. (2003, methodology): “4C; Passner et al. 1999; Piper et al. 1999).”
Functional specificity of a Hox protein mediated by the recognition of minor groove structure. (2007, unknown): “…typically disordered in the existing NMR and crystal structures (Billeter et al., 1993; Fraenkel and Pabo, 1998; Fraenkel et al., 1998; Hirsch and Aggarwal , 1995; Hovde et al., 2001; Li et al., 1995; Passner et al., 1999; Piper et al., 1999; Tucker-Kellogg et al., 1997; Wolberger et al., 1991).”
Structural Basis for Sequence Specific DNA Binding and Protein Dimerization of HOXA13 (2011, background): “By contrast, a methionine substituted in place of valine at this position in HOXB1 makes very different contacts in the major groove [9].”
Origins of specificity in protein-DNA recognition (2010, unknown): “Notable examples are Hox-Exd/Pbx heterodimers (28, 29, 214), the MATa1-MATα2 heterodimer (144), and the NFAT-Fos-Jun heterotrimer (215).”