2nxx | pdb_00002nxx
Crystal Structure of the Ligand-Binding Domains of the T.castaneum (Coleoptera) Heterodimer EcrUSP Bound to Ponasterone A
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| 2nxx, resolution 2.750Å | |||||||||||||
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| Ligands: | P1A | ||||||||||||
| Gene: | Ultraspiracle (USP) (Tribolium castaneum), Ecdysone Receptor (EcR) (Tribolium castaneum) | ||||||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Overview
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.
About this Structure
2NXX is a Protein complex structure of sequences from Tribolium castaneum. Full crystallographic information is available from OCA.
Reference
Structural and functional characterization of a novel type of ligand-independent RXR-USP receptor., Iwema T, Billas IM, Beck Y, Bonneton F, Nierengarten H, Chaumot A, Richards G, Laudet V, Moras D, EMBO J. 2007 Aug 22;26(16):3770-82. Epub 2007 Aug 2. PMID:17673910
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