Specificity of DNA-binding by PBX-HOX

The question arises as to whether the YPWM can confer specificity in HOX-PBX interactions. There are minor variations to the motif that could play such a role. Arguing against this notion, however, several different YPWM peptides interact with the PBX homeodomain in the same way (Sprules et al., 2000). Residues flanking the YPWM are conserved within paralog groups (Neuteboom et al., 

1995 Shanmugam et al., 1997 Sharkey et al., 1997 Morgan et al., 2000) and influence the stability of PBX-HOX complexes on co-operative binding sites that differ at position six (Shanmugam et al., 1997). These amino acids could modulate interactions with PBX by inducing conformational changes in the PBX homeodomain. 

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