Wu Wenjie, LoVerde Philip T
Departments of Biochemistry and Structural Biology and Pathology and Laboratory Medicine, University of Texas Health Sciences Center, San Antonio, TX, 78229-3800, USA.
Departments of Biochemistry and Structural Biology and Pathology and Laboratory Medicine, University of Texas Health Sciences Center, San Antonio, TX, 78229-3800, USA.
Mol Biochem Parasitol. 2019 Oct;233:111218. doi: 10.1016/j.molbiopara.2019.111218. Epub 2019 Aug 27.
Nuclear receptors (NRs) belong to a large protein superfamily which includes intracellular receptors for secreted hydrophobic signal molecules, such as steroid hormones and thyroid hormones. They regulate development and reproduction in metazoans by binding to the promoter region of their target gene to activate or repress mRNA synthesis. Isolation and characterization of NRs in the parasitic trematode Schistosoma mansoni identified two homologues of mammalian thyroid receptor (TR). This was the first known protostome exhibiting TR homologues. Three novel NRs each possess a novel set of two DNA binding domains (DBD) in tandem with a ligand binding domain (LBD) (2DBD-NRs) isolated in Schistosoma mansoni revealed a novel NR modular structure: A/B-DBD-DBD-hinge-LBD. Full length cDNA of several NRs have been isolated and studied in the parasitic trematodes S. mansoni, S. japonicum and in the cestode Echinococcus multilocularis. The genome of the blood flukes S. mansoni, S. japonicum and S. haematobium, the liver fluke Clonorchis sinensis and the cestode Echinococcus multilocularis have been sequenced. Study of the NR complement in parasitic Platyhelminths will help us to understand the role of NRs in regulation of their development and understand the evolution of NR in animals.
核受体(NRs)属于一个大型蛋白质超家族,其中包括分泌型疏水信号分子(如类固醇激素和甲状腺激素)的细胞内受体。它们通过与靶基因的启动子区域结合来激活或抑制mRNA合成,从而调节后生动物的发育和繁殖。在寄生吸虫曼氏血吸虫中分离和鉴定核受体,发现了两种哺乳动物甲状腺受体(TR)的同源物。这是已知的首个具有TR同源物的原口动物。在曼氏血吸虫中分离出的三种新型核受体,每种都具有一组新的两个串联的DNA结合结构域(DBD)和一个配体结合结构域(LBD)(2DBD-NRs),揭示了一种新型的核受体模块化结构:A/B-DBD-DBD-铰链-LBD。几种核受体的全长cDNA已在寄生吸虫曼氏血吸虫、日本血吸虫以及绦虫多房棘球绦虫中分离和研究。曼氏血吸虫、日本血吸虫和埃及血吸虫、华支睾吸虫以及多房棘球绦虫的基因组已被测序。对寄生扁形动物中核受体互补情况的研究将有助于我们了解核受体在其发育调控中的作用,并了解动物中核受体的进化。