Structural and functional divergence of a nuclear receptor of the RXR family from the trematode parasite Schistosoma mansoni
Structural and functional divergence of a nuclear receptor of the RXR family from the trematode parasite Schistosoma mansoni
复制标题
DOI：
10.1046/j.1432-1327.2000.01344.x
复制
发表时间：
2000-06-01
期刊：
影响因子：
--
通讯作者：
Laudet, V
中科院分区：
文献类型：
--
作者：
de Mendonça, RL;Escriva, H;Laudet, V
作者报道了曼氏血吸虫（Schistosoma mansoni）核受体超家族新成员（SmRXR; NR2B4-B）的克隆和功能特征，该家族是脊椎动物类维甲酸- x受体的同源物。SmRXR的dna结合C结构域与人类RXR α和果蝇超棘（USP）的同源性为80%，而与配体结合E结构域的同源性为22-25%。系统发育分析表明SmRXR属于RXR类群，是该分支的一个早期分支。SmRXR mRNA在所有生命周期阶段均有表达，但在自由生活的幼虫阶段表达水平较高。然而，SmRXR蛋白的表达水平明显不同，在卵中几乎不存在，而在血吸虫中浓度最高。重组SmRXR无论是单独结合，还是作为异源二聚体与小鼠视黄酸受体α或果蝇蜕皮激素受体结合，都不能与共识的直接重复反应元件结合。然而，嵌合结构的使用表明，SmRXR的C结构域将作为异源二聚体结合到传统的应答元件上，并且其特异性被D和E结构域的存在所修饰。根据这些结果，在哺乳动物细胞系共转染后，天然SmRXR未能反激活一个报告基因的转录。
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 RXR alpha 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.