tailieunhanh - Báo cáo Y học: A functionally conserved member of the FTZ-F1 nuclear receptor family from Schistosoma mansoni

Thefushi tarazu factor 1 (FTZ-F1) nuclear receptor sub-family comprises orphan receptors with crucial roles in development and sexual differentiation in vertebrates and invertebrates. We describe the structure and functional properties of an FTZ-F1 from the platyhelminth parasite of humans,Schistosoma mansoni, the first receptor from this family tobe characterized inaLophotrochozoan. It contains awell conservedDNA-binding domain (55–63%identity to other family members) and a poorly conserved ligand-binding domain (20% identity to that of zebrafish FF1a) | Eur. J. Biochem. 1-12 2002 FEBS 2002 doi A functionally conserved member of the FTZ-F1 nuclear receptor family from Schistosoma mansoni Ricardo L de Mendonca 1 Didier Bouton1 t Benjamin Bertin1 Hector Escriva2 Christophe Noel1 B B 4 B BF . B B B B B B BF B B B BB BB B BF BF BB BF BF BF BB BF B B BB BF B BB w B BB B BF B B B bB b BF BB B Jean-Marc Vanacker2 Jocelyne Cornette1 Vincent Laudet2 and Raymond J. Pierce1 1INSERM U 547 Institut Pasteur Lille France 2CNRS UMR 49 Ecole Normale Superieure de Lyon Lyon France The fushi tarazu factor 1 FTZ-F1 nuclear receptor subfamily comprises orphan receptors with crucial roles in development and sexual differentiation in vertebrates and invertebrates. We describe the structure and functional properties of an FTZ-F1 from the platyhelminth parasite of humans Schistosoma mansoni the first receptor from this family to be characterized in a Lophotrochozoan. It contains a well conserved DNA-binding domain 55-63 identity to other family members and a poorly conserved ligandbinding domain 20 identity to that of zebrafish FF1a . However both the ligand domain signature sequence and the activation function 2-activation domain AF2-AD are perfectly conserved. Phylogenetic analysis confirmed that SmFTZ-F1 is a member of nuclear receptor subfamily 5 but that it clustered with the Drosophila receptor DHR39 and has consequently been named NR5B1. The gene showed a complex structure with 10 exons and an overall size of kb. Two major transcripts were detected involving alternative promoter usage and splicing of the two 5 exons but which encoded identical proteins. SmFTZ-F1 mRNA is expressed at all life-cycle stages with the highest amounts in the larval forms miracidia sporocysts and cercariae . However expression of the protein showed a different pattern low in miracidia and higher in adult male worms. The protein bound the same monomeric response element as mammalian SF-1 SF-1 response element SFRE and .