{"doi":"10.1101/2022.01.04.474980","title":"The formation of a fuzzy complex in the negative arm regulates the robustness of the circadian clock","abstract":"Summary The circadian clock times cellular processes to the day/night cycle via a Transcription-Translation negative Feedback Loop (TTFL). However, a mechanistic understanding of the negative arm in both the timing of the TTFL and its control of output is lacking. We posited that the formation of negative-arm protein complexes was fundamental to clock regulation stemming from the negative arm. Using a modified peptide microarray approach termed L inear m o tif dis c overy using r at ional d e sign (LOCATE), we characterized the interaction of the disordered negative-arm clock protein FREQUENCY to its partner protein FREQUENCY-Interacting RNA helicase. LOCATE identified a specific Short Linear Motif (SLiM) and interaction “hotspot” as well as positively charged “islands” that mediate electrostatic interactions, suggesting a model where negative arm proteins form a “fuzzy” complex essential for clock timing and robustness. Further analysis revealed that the positively charged islands were an evolutionarily conserved feature in higher eukaryotes and contributed to proper clock function.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":297025,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9606,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":550645,"name":"Daniel Griffith","orcid":"0000-0002-9633-9601","position":1,"is_corresponding":false},{"id":984493,"name":"Divya G. Shastry","orcid":"0000-0002-0008-3681","position":2,"is_corresponding":false},{"id":322747,"name":"Jacqueline F. Pelham","orcid":"0000-0002-2268-3012","position":3,"is_corresponding":false},{"id":571142,"name":"Garrett M. Ginell","orcid":"0000-0001-6511-5480","position":4,"is_corresponding":false},{"id":984494,"name":"Joshua Thomas","orcid":"0000-0003-4659-1427","position":5,"is_corresponding":false},{"id":984495,"name":"Pankaj Karande","orcid":"0000-0002-9835-3108","position":6,"is_corresponding":false},{"id":107330,"name":"Alex S. Holehouse","orcid":"0000-0002-4155-5729","position":7,"is_corresponding":false},{"id":322748,"name":"Jennifer Hurley","orcid":"0000-0002-1085-9391","position":8,"is_corresponding":false},{"id":984492,"name":"Meaghan S. Jankowski","orcid":"0000-0002-3535-4373","position":0,"is_corresponding":true}],"reference_count":138,"raw_metadata":null,"created_at":"2026-07-19T00:31:21.257700Z","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":[]}