A Silent Partner

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Science  07 Sep 2007:
Vol. 317, Issue 5843, pp. 1297
DOI: 10.1126/science.317.5843.1297c

Like the vertebrate retinoid X receptors (RXRs) that it structurally and functionally resembles, the arthropod protein ultraspiracle (USP) heterodimerizes with other nuclear receptors to activate transcription of target genes. Various substances activate RXRs and have been postulated to serve as endogenous ligands, and the USP binding partner EcR (ecdysone receptor) is activated by ecdysone. Noting the similarity between the ligand-binding domain of USP in arthropods that are not Mecopterida (which includes the flies and moths) to that of the RXR, Iwema et al. cloned USP from the beetle Tribolium castaneum (TcUSP) as a representative non-Mecopterida USP. RXR ligands failed to activate a protein containing the TcUSP D/E domains (regions important for ligand binding and heterodimerization), and electrospray ionization mass spectrometric analysis indicated that TcUSP failed to bind RXR ligands in vitro. Analysis of the crystal structure of the TcUSP ligand-binding domain in the context of a functional TcUSP-EcR heterodimer indicated that TcUSP exhibited a stable apo structure in an inactive antagonist conformation, which did not have a conventional ligand-binding pocket. Phylogenetic analysis emphasized the evolutionary plasticity of the RXR-USP-family ligand-binding domain, suggesting that even though non-Mecopterida USP does not, RXRs do indeed bind endogenous ligands. — EMA

EMBO J. 26, 3770 (2007).

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