Structural and functional divergence of a nuclear receptor of the RXR family from the trematode parasite Schistosoma mansoni

We describe the cloning and functional characterization of Schistosoma mans oni retinoid-X-receptor (SmRXR; NR2B4-B), a novel member of the nuclear rec eptor superfamily from S. mansoni, a homologue of vertebrate retinoid-X-rec eptor. The DNA-binding C domain of SmRXR shows 80% sequence identity to bot h human RXR alpha and Drosophila ultraspiracle (USP), but a much lower leve l of conservation of the ligand-binding E domain (22-25% identity). Phyloge netic analysis places SmRXR within the RXR group as an early offshoot of th is clade. SmRXR mRNA is expressed at all life-cycle stages but at higher le vels in the free-living larval stages. However, the SmRXR protein is expres sed at markedly different levels, being almost absent from eggs while prese nt at the highest concentration in schistosomula. Recombinant SmRXR fails t o bind to the consensus direct repeat response elements, either alone, or a s a heterodimer with mouse retinoic acid receptor alpha or the Drosophila e cdysone receptor. However, the use of chimaeric constructions shows that th e C domain of SmRXR will bind to conventional response elements as a hetero dimer, and that its specificity is modified by the presence of the D and E domains. In accordance with these results, native SmRXR failed to transacti vate the transcription of a reporter gene after cotransfection of mammalian cell lines.