Figure 1
Identification of alternative TALE interaction interface(s) in the human HOXA9 protein. (A) Schematic representation of HOXA9, PBX1 and MEIS1, with protein domains and motifs involved in the formation of dimeric or trimeric complexes. The hexapeptide (HX) is indicated. The three PYP residues of the PBX1 homeodomain (HD) participate in the formation of an hydrophobic pocket that interacts with the conserved Trp (W) residue of the HX motif, as determined by the HOXA9/PBX1 crystal structure13. Domains of interaction between PBX1 (PBCA and PBCB) and MEIS1 (MEISA and MEISB) proteins are also indicated. The right panel illustrates the formation of dimeric (upper) and trimeric (lower) complexes between HOXA9 and PBX1 or HOXA9, PBX1 and MEIS1, respectively. The characterized interaction between the conserved Trp residue of the HOXA9 HX and the hydrophobic pocket formed in part by the PYP residues of PBX1 is indicated. Question mark highlights the role of additional uncharacterized binding interface(s) in HOXA9 that could be involved in the interaction with PBX1 and MEIS1 in the trimeric complex. (B) Schematic diagram of HOXA9 that represents predicted short linear interaction motifs (SLiMs, green bars), organized domains (brown blocks) and disordered regions (blue waves). The level of conservation of each residue among vertebrate HOXA9 sequences is also indicated (red bars). A diagram of HOXA9 summarizes the prediction of SLiMs (bars) and organized domains (white boxes). The deletion of the first 187 residues is indicated (dN187). This structure prediction was obtained with SliMPred32. (C) Schematic representation of the HOXA9 constructs analyzed with the TALE cofactors in this study. Fusions with Venus fragments are voluntarily not indicated (see also Table 1). Mutations are indicated and highlighted with a black bar. HOXA9 and HOXA1 protein fragments are in red or blue, respectively.
