{"doi":"10.1210/me.2006-0179","title":"Definition of the Molecular Basis for Estrogen Receptor-Related Receptor-α-Cofactor Interactions","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Estrogen receptor-related receptor-α (ERRα) is an orphan nuclear receptor that does not appear to require a classical small molecule ligand to facilitate its interaction with coactivators and/or hormone response elements within target genes. Instead, the apo-receptor is capable of interacting in a constitutive manner with coactivators that stimulate transcription by acting as protein ligands. We have screened combinatorial phage libraries for peptides that selectively interact with ERRα to probe the architecture of the ERRα-coactivator pocket. In this manner, we have uncovered a fundamental difference in the mechanism by which this receptor interacts with peroxisome proliferator-activated receptor-γ coactivator-1α, as compared with members of the steroid receptor coactivator subfamily of coactivators. Our findings suggest that it may be possible to develop ERRα ligands that exhibit different pharmacological activities as a consequence of their ability to differentially regulate coactivator recruitment. In addition, these findings have implications beyond ERRα because they suggest that subtle alterations in the structure of the activation function-2 pocket within any nuclear receptor may enable differential recruitment of coactivators, an observation of notable pharmaceutical importance.</jats:p>","journal":"Molecular Endocrinology","year":2007,"id":46600,"datarank":2.582497659267556,"base_score":4.07753744390572,"endowment":4.07753744390572,"self_citation_contribution":0.611630616585858,"citation_network_contribution":1.9708670426816979,"self_endowment_contribution":0.611630616585858,"citer_contribution":1.9708670426816979,"corpus_percentile":null,"corpus_rank":null,"citation_count":58,"citer_count":53,"citers_with_citation_signal":46,"citers_with_endowment":46,"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":215880,"name":"Mary A. Dwyer","orcid":null,"position":1,"is_corresponding":false},{"id":143892,"name":"Donald P. McDonnell","orcid":null,"position":2,"is_corresponding":false},{"id":215879,"name":"Stéphanie Gaillard","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Definition of the Molecular Basis for Estrogen Receptor-Related Receptor-α-Cofactor Interactions","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Estrogen receptor-related receptor-α (ERRα) is an orphan nuclear receptor that does not appear to require a classical small molecule ligand to facilitate its interaction with coactivators and/or hormone response elements within target genes. Instead, the apo-receptor is capable of interacting in a constitutive manner with coactivators that stimulate transcription by acting as protein ligands. We have screened combinatorial phage libraries for peptides that selectively interact with ERRα to probe the architecture of the ERRα-coactivator pocket. In this manner, we have uncovered a fundamental difference in the mechanism by which this receptor interacts with peroxisome proliferator-activated receptor-γ coactivator-1α, as compared with members of the steroid receptor coactivator subfamily of coactivators. Our findings suggest that it may be possible to develop ERRα ligands that exhibit different pharmacological activities as a consequence of their ability to differentially regulate coactivator recruitment. In addition, these findings have implications beyond ERRα because they suggest that subtle alterations in the structure of the activation function-2 pocket within any nuclear receptor may enable differential recruitment of coactivators, an observation of notable pharmaceutical importance.</jats:p>","is_dataset_classified":null,"base_score":4.07753744390572,"endowment":4.07753744390572,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17053040","pmcid":null,"openalex_id":"https://openalex.org/W2077994082","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"DK074307","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK62434","title":null}],"total_grants":2,"fwci":3.1192,"citation_percentile":0.91621599,"influential_citations":2,"citation_trend":[{"year":2012,"count":6},{"year":2013,"count":1},{"year":2014,"count":1},{"year":2015,"count":1},{"year":2017,"count":3},{"year":2019,"count":2},{"year":2020,"count":5},{"year":2021,"count":2},{"year":2022,"count":1},{"year":2023,"count":4},{"year":2024,"count":1},{"year":2025,"count":3}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://academic.oup.com/mend/article-pdf/21/1/62/8958767/mend0062.pdf","host_type":"journal"},{"url":"https://doi.org/10.1210/me.2006-0179","host_type":"BRONZE"},{"url":"https://academic.oup.com/mend/article-pdf/21/1/62/8958767/mend0062.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/mend/article-pdf/21/1/62/8958767/mend0062.pdf","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17053040","host_type":"repository"}],"fields_of_study":["Estrogen and related hormone effects","Receptor Mechanisms and Signaling","Monoclonal and Polyclonal Antibodies Research","Biology","Chemistry","Medicine","Amino Acid Motifs","Amino Acid Sequence","HeLa Cells","Humans","Ligands","Models, Molecular","Molecular Sequence Data","Peptide Library","Promoter Regions, Genetic","Protein Binding","Protein Structure, Tertiary","Receptors, Estrogen","Transcription Factors","Transcription, Genetic","Two-Hybrid System Techniques","ERRalpha Estrogen-Related Receptor"],"mesh_terms":["ERRalpha Estrogen-Related Receptor","Amino Acid Sequence","HeLa Cells","Humans","Ligands","Models, Molecular","Molecular Sequence Data","Promoter Regions, Genetic","Protein Binding","Receptors, Estrogen","Transcription Factors","Transcription, Genetic","Protein Structure, Tertiary","Peptide Library","Two-Hybrid System Techniques","Amino Acid Motifs","Hela Cells"],"keywords":["Coactivator","Nuclear receptor coactivator 2","Nuclear receptor coactivator 3","Nuclear receptor","Nuclear receptor coactivator 1","Biology","Estrogen-related receptor gamma","Estrogen-related receptor alpha","Neuron-derived orphan receptor 1","Nuclear receptor co-repressor 1","Cell biology","Receptor","Enzyme-linked receptor","Transcription factor","5-HT5A receptor","PELP-1","Estrogen receptor","Genetics","Gene"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-12T01:45:07.639417Z","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":[]}