{"doi":"10.1073/pnas.1615310114","title":"Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>Circadian rhythms depend upon the precise coordination of protein interactions within the transcription–translation feedback loop of the molecular clock. Period (PER) and cryptochrome (CRY) rhythmically repress activity of the circadian transcription factor, CLOCK:BMAL1 (brain and muscle Arnt-like protein 1), to establish daily patterns of gene expression. CRY1 binds to CLOCK:BMAL1 with and without PER to inhibit CLOCK:BMAL1 activity. Here we show that CRY1 interacts with the CLOCK PAS-B domain to dock the transcription factor into the secondary pocket of CRY1. Studies of a CRY1:CLOCK:BMAL1 complex highlight critical interfaces for the direct regulation of CLOCK:BMAL1 by cryptochromes. A molecular understanding of the clock mechanism is fundamental for the development and application of therapies for circadian-related disorders.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2017,"id":626799,"datarank":0.7379971388742189,"base_score":4.919980925828125,"endowment":4.919980925828125,"self_citation_contribution":0.7379971388742189,"citation_network_contribution":0.0,"self_endowment_contribution":0.7379971388742189,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":136,"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":301884,"name":"Jennifer L. Fribourgh","orcid":"0000-0001-5954-4991","position":1,"is_corresponding":false},{"id":1442318,"name":"Yogarany Chelliah","orcid":null,"position":2,"is_corresponding":false},{"id":301886,"name":"Colby R. Sandate","orcid":"0000-0002-8758-5931","position":3,"is_corresponding":false},{"id":628556,"name":"Greg L. Hura","orcid":"0000-0003-0501-8464","position":4,"is_corresponding":false},{"id":188091,"name":"Dina Schneidman-Duhovny","orcid":null,"position":5,"is_corresponding":false},{"id":285738,"name":"Sarvind Tripathi","orcid":"0000-0002-6959-0577","position":6,"is_corresponding":false},{"id":287849,"name":"Joseph S. Takahashi","orcid":"0000-0003-0384-8878","position":7,"is_corresponding":false},{"id":1120099,"name":"Carrie L. Partch","orcid":"0000-0002-0327-3448","position":8,"is_corresponding":false},{"id":301887,"name":"Alicia K. 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Studies of a CRY1:CLOCK:BMAL1 complex highlight critical interfaces for the direct regulation of CLOCK:BMAL1 by cryptochromes. A molecular understanding of the clock mechanism is fundamental for the development and application of therapies for circadian-related disorders.</jats:p>","is_dataset_classified":null,"base_score":4.919980925828125,"endowment":4.919980925828125,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28143926","pmcid":"PMC5321004","openalex_id":"https://openalex.org/W2583671727","authors":[],"funders":[{"funder_name":"HHS | National Institutes of Health","grant_id":"GM107069","title":null},{"funder_name":"HHS | National Institutes of Health","grant_id":"CA189660","title":null},{"funder_name":"Howard Hughes Medical Institute","grant_id":"HHMI","title":null},{"funder_name":"NCI NIH HHS","grant_id":"F31 CA189660","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM107069","title":null}],"total_grants":5,"fwci":5.141,"citation_percentile":0.96510041,"influential_citations":0,"citation_trend":[{"year":2017,"count":6},{"year":2018,"count":10},{"year":2019,"count":13},{"year":2020,"count":17},{"year":2021,"count":16},{"year":2022,"count":18},{"year":2023,"count":17},{"year":2024,"count":10},{"year":2025,"count":20},{"year":2026,"count":9}],"oa_status":"bronze","license":"http://www.pnas.org/site/misc/userlicense.xhtml","oa_locations":[{"url":"https://www.pnas.org/content/pnas/114/7/1560.full.pdf","host_type":"journal"},{"url":"https://www.pnas.org/content/pnas/114/7/1560.full.pdf","host_type":"publisher"},{"url":"http://www.pnas.org/syndication/doi/10.1073/pnas.1615310114","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.1615310114","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.1615310114","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28143926","host_type":"repository"},{"url":"https://www.osti.gov/biblio/1379737","host_type":"repository"},{"url":"https://escholarship.org/uc/item/6qn5g17m","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5321004","host_type":"repository"},{"url":"http://www.escholarship.org/uc/item/6qn5g17m","host_type":"repository"},{"url":"https://www.osti.gov/servlets/purl/1379737","host_type":"repository"}],"fields_of_study":["Circadian rhythm and melatonin","Light effects on plants","Spaceflight effects on biology"],"mesh_terms":["Protein Domains","Amino Acid Sequence","Animals","Binding Sites","Models, Molecular","Mutation","Protein Binding","Crystallography, X-Ray","Spodoptera","Mice","CLOCK Proteins","ARNTL Transcription Factors","Cryptochromes","Circadian Clocks","Sf9 Cells"],"keywords":["Cryptochrome","Circadian clock","Circadian rhythm","Biology","Cell biology","Oscillating gene","Transcription factor","Transcription (linguistics)","CLOCK","Genetics","Aryl hydrocarbon receptor nuclear translocator","E-box","Timeless","Period (music)","Neuroscience","Gene","Physics","Circadian rhythms","Integrative Modeling","Pas Domains"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T15:16:26.131878Z","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":[]}