DIFFERENCES IN DNA-SEQUENCE RECOGNITION BY THE HEAT-SHOCK FACTORS OF DROSOPHILA-MELANOGASTER AND THE PARASITIC HELMINTH SCHISTOSOMA-MANSONI

It was recently shown that schistosome extracts contain heat-shock fac tor (HSF) activity that correlates with the pattern of hsp70 mRNA leve ls at different developmental stages of the parasite (Levy-Holtzman an d Schechter (1993) Parasitology 108, 35-42). To extend our understandi ng of the HSF activity revealed in extracts of Schistosoma mansoni (Sm ), it was further analyzed by competition experiments and compared wit h the well characterized HSF of Drosophila melanogaster (Dm. The inter actions of HSF in Sm extracts (SmHSF) and HSF of Dm (DmHSF) with P-32- labeled heat shock element (HSE) probes, with and without unlabeled co mpetitor DNA probes (HSE-related oligos), were analyzed by gel retarda tion assay. The binding and inhibition studies demonstrated that SmHSF and DmHSF differ in HSE sequence recognition: an array of three nGAAn inverted repeats according to the ideal consensus sequence (nGAAnnTTC nnGAAn) is recognized by DmHSF, but not by SmHSF. In the schistosome, binding is attained only when the third pentamer is a variant, compose d of nGTAn instead of nGAAn. The presence of this variant in the promo ter of the hsp70 gene of the parasite suggests coevolution of the vari ant sequence together with the SmHSF which interacts efficiently with the variant, but not with the ideal HSE sequence. Further inhibition s tudies revealed additional differences between SmHSF and DmHSF in reco gnition of the first and second nGAAn pentamers of HSE. In analogy to other systems of ligand-protein interactions, we propose that the comp lementarity between the HSE ligand and the HSF protein is higher in Sm HSF, as compared to DmHSF.