{"doi":"10.1073/pnas.98.4.1549","title":"The structure of the ultraspiracle ligand-binding domain reveals a nuclear receptor locked in an inactive conformation","abstract":"<jats:p>\n                    Ultraspiracle (USP) is the invertebrate homologue of the\n mammalian retinoid X receptor (RXR). RXR plays a uniquely important\n role in differentiation, development, and homeostasis through its\n ability to serve as a heterodimeric partner to many other nuclear\n receptors. RXR is able to influence the activity of its partner\n receptors through the action of the ligand 9-\n                    <jats:italic>cis</jats:italic>\n                    retinoic acid. In contrast to RXR, USP has no known high-affinity\n ligand and is thought to be a silent component in the heterodimeric\n complex with partner receptors such as the ecdysone receptor. Here we\n report the 2.4-Å crystal structure of the USP ligand-binding domain.\n The structure shows that a conserved sequence motif found in dipteran\n and lepidopteran USPs, but not in mammalian RXRs, serves to lock USP in\n an inactive conformation. It also shows that USP has a large\n hydrophobic cavity, implying that there is almost certainly a natural\n ligand for USP. This cavity is larger than that seen previously for\n most other nuclear receptors. Intriguingly, this cavity has partial\n occupancy by a bound lipid, which is likely to resemble the natural\n ligand for USP.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2001,"id":627296,"datarank":0.7612760722850741,"base_score":5.075173815233827,"endowment":5.075173815233827,"self_citation_contribution":0.7612760722850741,"citation_network_contribution":0.0,"self_endowment_contribution":0.7612760722850741,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":159,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1623504,"name":"Sew Y. Peak-Chew","orcid":null,"position":1,"is_corresponding":false},{"id":80488,"name":"Ronald M. Evans","orcid":"0000-0002-9986-5965","position":2,"is_corresponding":false},{"id":69,"name":"John W. R. Schwabe","orcid":"0000-0003-2865-4383","position":3,"is_corresponding":false},{"id":1623502,"name":"Gina M. Clayton","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The structure of the ultraspiracle ligand-binding domain reveals a nuclear receptor locked in an inactive conformation","abstract":"<jats:p>\n                    Ultraspiracle (USP) is the invertebrate homologue of the\n mammalian retinoid X receptor (RXR). RXR plays a uniquely important\n role in differentiation, development, and homeostasis through its\n ability to serve as a heterodimeric partner to many other nuclear\n receptors. RXR is able to influence the activity of its partner\n receptors through the action of the ligand 9-\n                    <jats:italic>cis</jats:italic>\n                    retinoic acid. In contrast to RXR, USP has no known high-affinity\n ligand and is thought to be a silent component in the heterodimeric\n complex with partner receptors such as the ecdysone receptor. Here we\n report the 2.4-Å crystal structure of the USP ligand-binding domain.\n The structure shows that a conserved sequence motif found in dipteran\n and lepidopteran USPs, but not in mammalian RXRs, serves to lock USP in\n an inactive conformation. It also shows that USP has a large\n hydrophobic cavity, implying that there is almost certainly a natural\n ligand for USP. This cavity is larger than that seen previously for\n most other nuclear receptors. Intriguingly, this cavity has partial\n occupancy by a bound lipid, which is likely to resemble the natural\n ligand for USP.\n                  </jats:p>","is_dataset_classified":null,"base_score":4.727387818712341,"endowment":4.727387818712341,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11171988","pmcid":"PMC29294","openalex_id":"https://openalex.org/W4236233796","authors":[],"funders":[],"total_grants":0,"fwci":3.9125,"citation_percentile":0.94391418,"influential_citations":0,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":5},{"year":2014,"count":4},{"year":2015,"count":3},{"year":2016,"count":1},{"year":2017,"count":3},{"year":2018,"count":3},{"year":2019,"count":2},{"year":2020,"count":1},{"year":2021,"count":3},{"year":2023,"count":1},{"year":2024,"count":1},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://pnas.org/doi/pdf/10.1073/pnas.98.4.1549","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.98.4.1549","host_type":"journal"}],"fields_of_study":["Retinoids in leukemia and cellular processes","Neurobiology and Insect Physiology Research","Antioxidant Activity and Oxidative Stress","Amino Acid Sequence","Animals","Crystallography, X-Ray","DNA-Binding Proteins","Drosophila Proteins","Drosophila melanogaster","Humans","Ligands","Lipid Metabolism","Mice","Models, Molecular","Molecular Sequence Data","Protein Structure, Secondary","Receptors, Steroid","Sequence Homology, Amino Acid","Transcription Factors"],"mesh_terms":["Animals","Humans","Mice","Drosophila melanogaster","DNA-Binding Proteins","Drosophila Proteins","Receptors, Steroid","Transcription Factors","Ligands","Crystallography, X-Ray","Amino Acid Sequence","Protein Structure, Secondary","Sequence Homology, Amino Acid","Models, Molecular","Molecular Sequence Data","Lipid Metabolism"],"keywords":["Retinoid X receptor","Nuclear receptor","Ecdysone receptor","Receptor","Biology","Retinoic acid","Ligand (biochemistry)","Cell biology","Biochemistry","Transcription factor","Gene"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"},{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T17:00:55.245802Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}