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Article Dans Une Revue EMBO Journal Année : 2007

Structural and functional characterization of a novel type of ligand-independent RXR-USP receptor

Caractérisation structurale et fonctionelle d'un nouveau type ligand-indépendant de récepteur RXR-USP

Résumé

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 broad 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 phylogenetical analysis suggest that RXR-USPs have undergone remarkable functional shifts during evolution and give insight into receptor-ligand binding evolution and dynamics.

Dates et versions

hal-02589453 , version 1 (15-05-2020)

Identifiants

Citer

T. Iwema, I.M. Billas, Y. Beck, François Bonneton, H. Nierengarten, et al.. Structural and functional characterization of a novel type of ligand-independent RXR-USP receptor. EMBO Journal, 2007, 26 (16), pp.3770-3782. ⟨10.1038/sj.emboj.7601810⟩. ⟨hal-02589453⟩
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