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 mansoni retinoid-X-receptor (SmRXR; NR2B4-B), a novel member of the nuclear receptor superfamily from S. mansoni, a homologue of vertebrate retinoid-X-receptor. The DNA-binding C domain of SmRXR shows 80% sequence identity to both human RXRalpha and Drosophila ultraspiracle (USP), but a much lower level of conservation of the ligand-binding E domain (22-25% identity). Phylogenetic analysis places SmRXR within the RXR group as an early offshoot of this clade. SmRXR mRNA is expressed at all life-cycle stages but at higher levels in the free-living larval stages. However, the SmRXR protein is expressed at markedly different levels, being almost absent from eggs while present at the highest concentration in schistosomula. Recombinant SmRXR fails to bind to the consensus direct repeat response elements, either alone, or as a heterodimer with mouse retinoic acid receptor alpha or the Drosophila ecdysone receptor. However, the use of chimaeric constructions shows that the C domain of SmRXR will bind to conventional response elements as a heterodimer, and that its specificity is modified by the presence of the D and E domains. In accordance with these results, native SmRXR failed to transactivate the transcription of a reporter gene after cotransfection of mammalian cell lines.
de Mendonça
R L
RL
INSERM U 167, Institut Pasteur, Lille; CNRS UMR 49, Ecole Normale Supérieure de Lyon, France.
Escriva
H
H
Bouton
D
D
Zelus
D
D
Vanacker
J M
JM
Bonnelye
E
E
Cornette
J
J
Pierce
R J
RJ
Laudet
V
V
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D004331:Drosophila melanogaster / Q000737:chemistry; D004531:Eggs / Q000032:analysis; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006801:Humans; D007814:Larva / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D020033:Protein Isoforms / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary; D051381:Rats; D011916:Rats, Inbred F344; D018168:Receptors, Retinoic Acid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D047488:Retinoid X Receptors; D012550:Schistosoma mansoni / Q000235:genetics* / Q000254:growth & development; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
D020033:Protein Isoforms; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; C055469:ecdysone receptor; D004247:DNA