Structural and Functional Characterization of a Novel Type of Ligand-independent Rxr-usp Receptor.
From: IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), UMR7104 CNRS, U596 INSERM, ULP, Département de Biologie et de Génomique Structurales, Illkirch, France.
The EMBO journal
- Publish Date: Aug 2007
- ISSN: 0261-4189
- Volume: 26
- Issue: 16
- Pages: 3770-82
- Medium: Print
- Language: English
- Citation (JAMA): Iwema Thomas, Billas Isabelle M L, Beck Yannick, et al. Structural and Functional Characterization of a Novel Type of Ligand-independent Rxr-usp Receptor.. EMBO J. Aug 2007;26:3770-82
Abstract
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.
Mesh Headings (Keywords): Animals, Animals, Genetically Modified, Binding Sites, DNA-Binding Proteins, Dimerization, Drosophila melanogaster, Evolution, Molecular, Genes, Reporter, Humans, Insect Proteins, Ligands, Models, Molecular, Molecular Sequence Data, Phylogeny, Protein Structure, Quaternary, Receptors, Steroid, Retinoid X Receptor alpha, Transcription Factors, Tribolium
Check for Full Text / PubMed Unique Identifier (PMID): 17673910
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