Crystal Structure of the Ligand-binding Domain of the Ultraspiracle Protein USP, the Ortholog of Retinoid X Receptors in Insects

The major postembryonic developmental events happening in insect life, including molting and metamorphosis, are regulated and coordinated temporally by pulses of ecdysone. The biological activity of this steroid hormone is mediated by two nuclear receptors: the ecdysone receptor (EcR) and the Ultras...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-03, Vol.276 (10), p.7465-7474
Main Authors: Billas, IsabelleM.L., Moulinier, Luc, Rochel, Natacha, Moras, Dino
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Biochemistry, Molecular Biology
Crystallography, X-Ray
Heliothis virescens
Insect Proteins - chemistry
Insecta
Lepidoptera
Life Sciences
Ligands
Models, Molecular
Molecular Sequence Data
Noctuidae
Protein Binding
Protein Conformation
Protein Structure, Tertiary
Receptors, Retinoic Acid - metabolism
Retinoid X Receptors
Sequence Homology, Amino Acid
Transcription Factors - metabolism
Ultraspiracle Protein
USP
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Summary:The major postembryonic developmental events happening in insect life, including molting and metamorphosis, are regulated and coordinated temporally by pulses of ecdysone. The biological activity of this steroid hormone is mediated by two nuclear receptors: the ecdysone receptor (EcR) and the Ultraspiracle protein (USP). The crystal structure of the ligand-binding domain from the lepidopteran Heliothis virescens USP reported here shows that the loop connecting helices H1 and H3 precludes the canonical agonist conformation. The key residues that stabilize this unique loop conformation are strictly conserved within the lepidopteran USP family. The presence of an unexpected bound ligand that drives an unusual antagonist conformation confirms the induced-fit mechanism accompanying the ligand binding. The ligand-binding pocket exhibits a retinoid X receptor-like anchoring part near a conserved arginine, which could interact with a USP ligand functional group. The structure of this receptor provides the template for designing inhibitors, which could be utilized as a novel type of environmentally safe insecticides1G2N.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M008926200