The paired-domain regulates DNA binding by the homeodomain within the intact Pax-3 protein.

The Journal of Biological Chemistry
D Alan Underhill, Philippe Gros

Abstract

Pax-3 contains two structurally independent DNA-binding domains, a paired-domain and a homeodomain. Their functional interdependence has been suggested by the analysis of the Sp-delayed (Spd) mouse mutant, in which a glycine to arginine substitution at position 9 of the paired-domain abrogates DNA binding by both domains. This glycine is located in the beta-turn portion of a beta-hairpin motif, and the requirement for this structure was investigated by mutagenesis at this and neighboring positions. At position 9, only substitution with proline increased DNA binding by the paired-domain and homeodomain above the level observed with the Spd arginine mutation, suggesting that the beta-turn is necessary for the function of both DNA-binding domains. Alanine scanning mutagenesis also identified a number of flanking residues important for DNA binding by both domains, emphasizing the requirement of the beta-hairpin for the interaction of Pax-3 with DNA. Furthermore, we show that these mutations reduce binding by the homeodomain at the monomeric level and do not impair dimerization on a TAAT(N)2ATTA consensus motif. In contrast, the wild-type paired-domain was found to prevent dimerization on consensus motifs with 3-base pair spacing of...Continue Reading

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Citations

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