{"doi":"10.1126/science.1065249","title":"Structure, Function, and Activator-Induced Conformations of the CRSP Coactivator","abstract":"<jats:p>The human cofactor complexes ARC (activator-recruited cofactor) and CRSP (cofactor required for Sp1 activation) mediate activator-dependent transcription in vitro. Although these complexes share several common subunits, their structural and functional relationships remain unknown. Here, we report that affinity-purified ARC consists of two distinct multisubunit complexes: a larger complex, denoted ARC-L, and a smaller coactivator, CRSP. Reconstituted in vitro transcription with biochemically separated ARC-L and CRSP reveals differential cofactor functions. The ARC-L complex is transcriptionally inactive, whereas the CRSP complex is highly active. Structural determination by electron microscopy (EM) and three-dimensional reconstruction indicate substantial differences in size and shape between ARC-L and CRSP. Moreover, EM analysis of independently derived CRSP complexes reveals distinct conformations induced by different activators. These results suggest that CRSP may potentiate transcription via specific activator-induced conformational changes.</jats:p>","journal":"Science","year":2002,"id":669739,"datarank":11.372491102083485,"base_score":5.5909869805108565,"endowment":5.5909869805108565,"self_citation_contribution":0.8386480470766287,"citation_network_contribution":10.533843055006857,"self_endowment_contribution":0.8386480470766287,"citer_contribution":10.533843055006857,"corpus_percentile":null,"corpus_rank":null,"citation_count":267,"citer_count":200,"citers_with_citation_signal":198,"citers_with_endowment":198,"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":1749210,"name":"Anders M. Näär","orcid":null,"position":1,"is_corresponding":false},{"id":1749211,"name":"Frank Andel","orcid":null,"position":2,"is_corresponding":false},{"id":138918,"name":"Eva Nogales","orcid":null,"position":3,"is_corresponding":false},{"id":109375,"name":"Robert Tjian","orcid":"0000-0003-0539-8217","position":4,"is_corresponding":false},{"id":226578,"name":"Dylan J. Taatjes","orcid":"0000-0003-4444-5688","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Structure, Function, and Activator-Induced Conformations of the CRSP Coactivator","abstract":"<jats:p>The human cofactor complexes ARC (activator-recruited cofactor) and CRSP (cofactor required for Sp1 activation) mediate activator-dependent transcription in vitro. Although these complexes share several common subunits, their structural and functional relationships remain unknown. Here, we report that affinity-purified ARC consists of two distinct multisubunit complexes: a larger complex, denoted ARC-L, and a smaller coactivator, CRSP. Reconstituted in vitro transcription with biochemically separated ARC-L and CRSP reveals differential cofactor functions. The ARC-L complex is transcriptionally inactive, whereas the CRSP complex is highly active. Structural determination by electron microscopy (EM) and three-dimensional reconstruction indicate substantial differences in size and shape between ARC-L and CRSP. Moreover, EM analysis of independently derived CRSP complexes reveals distinct conformations induced by different activators. These results suggest that CRSP may potentiate transcription via specific activator-induced conformational changes.</jats:p>","is_dataset_classified":null,"base_score":5.5909869805108565,"endowment":5.5909869805108565,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11834832","pmcid":null,"openalex_id":"https://openalex.org/W2006936902","authors":[],"funders":[],"total_grants":0,"fwci":7.8761,"citation_percentile":0.9837433,"influential_citations":0,"citation_trend":[{"year":2012,"count":8},{"year":2013,"count":14},{"year":2014,"count":9},{"year":2015,"count":7},{"year":2016,"count":12},{"year":2017,"count":9},{"year":2018,"count":8},{"year":2019,"count":6},{"year":2020,"count":5},{"year":2021,"count":9},{"year":2022,"count":5},{"year":2023,"count":4},{"year":2024,"count":8},{"year":2025,"count":6},{"year":2026,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.science.org/doi/pdf/10.1126/science.1065249","host_type":"publisher"},{"url":"https://doi.org/10.1126/science.1065249","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11834832","host_type":"repository"}],"fields_of_study":["Ubiquitin and proteasome pathways","Cancer-related gene regulation","RNA modifications and cancer","CCAAT-Enhancer-Binding Proteins","Chromatin","DNA-Binding Proteins","HeLa Cells","Herpes Simplex Virus Protein Vmw65","Humans","Image Processing, Computer-Assisted","Imaging, Three-Dimensional","Macromolecular Substances","Microscopy, Electron","Models, Genetic","Precipitin Tests","Protein Binding","Protein Structure, Quaternary","Protein Structure, Tertiary","Protein Subunits","Recombinant Fusion Proteins","Recombinant Proteins","Sterol Regulatory Element Binding Protein 1","Trans-Activators","Transcription Factors","Transcription, Genetic","Transcriptional Activation"],"mesh_terms":["Chromatin","DNA-Binding Proteins","HeLa Cells","Humans","Image Processing, Computer-Assisted","Microscopy, Electron","Models, Genetic","Precipitin Tests","Protein Binding","Recombinant Fusion Proteins","Recombinant Proteins","Transcription Factors","Transcription, Genetic","Transcriptional Activation","Trans-Activators","Herpes Simplex Virus Protein Vmw65","Protein Structure, Tertiary","Protein Structure, Quaternary","Protein Subunits","Imaging, Three-Dimensional","CCAAT-Enhancer-Binding Proteins","Macromolecular Substances","Sterol Regulatory Element Binding Protein 1","Hela Cells"],"keywords":["Coactivator","Activator (genetics)","Cofactor","Chemistry","Transcription (linguistics)","In vitro","Transcription factor","Arc (geometry)","Cell biology","Biophysics","Stereochemistry","Biology","Biochemistry","Receptor","Enzyme","Gene","Geometry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-15T03:20:51.001264Z","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":[]}