期刊
EMBO JOURNAL
卷 26, 期 16, 页码 3770-3782出版社
WILEY-BLACKWELL
DOI: 10.1038/sj.emboj.7601810
关键词
constitutive activity; ligand binding; nuclear receptor; retinoid X receptor; ultraspiracle
Retinoid X receptor (RXR) and Ultraspiracle (USP) play a central role as ubiquitous heterodimerization partners of many nuclear receptors. While it has long been accepted that a wide range of ligands can activate vertebrate/ mollusc RXRs, the existence and necessity of specific endogenous ligands activating RXR- USP in vivo is still matter of intense debate. Here we report the existence of a novel type of RXR-USP with a ligand-independent functional conformation. Our studies involved Tribolium USP (TcUSP) as representative of most arthropod RXR-USPs, with high sequence homology to vertebrate/ mollusc RXRs. The crystal structure of the ligand- binding domain of TcUSP was solved in the context of the functional heterodimer with the ecdysone receptor (EcR). While EcR exhibits a canonical ligand- bound conformation, USP adopts an original apo structure. Our functional data demonstrate that TcUSP is a constitutively silent partner of EcR, and that none of the RXR ligands can bind and activate TcUSP. These findings together with a phylogenetic analysis suggest that RXR- USPs have undergone remarkable functional shifts during evolution and give insight into receptor-ligand binding evolution and dynamics.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据