{"doi":"10.1101/2020.07.04.187161","title":"Calmodulin acts as a state-dependent switch to control a cardiac potassium channel opening","abstract":"Abstract Calmodulin (CaM) and PIP 2 are potent regulators of the voltage-gated potassium channel KCNQ1 (K V 7.1), which conducts the I Ks current important for repolarization of cardiac action potentials. Although cryo-EM structures revealed intricate interactions between the KCNQ1 voltage-sensing domain (VSD), CaM, and PIP 2 , the functional consequences of these interactions remain unknown. Here, we show that CaM-VSD interactions act as a state-dependent switch to control KCNQ1 pore opening. Combined electrophysiology and molecular dynamics network analysis suggest that VSD transition into the fully-activated state allows PIP 2 to compete with CaM for binding to VSD, leading to the conformational change that alters the VSD-pore coupling. We identify a motif in the KCNQ1 cytosolic domain which works downstream of CaM-VSD interactions to facilitate the conformational change. Our findings suggest a gating mechanism that integrates PIP 2 and CaM in KCNQ1 voltage-dependent activation, yielding insights into how KCNQ1 gains the phenotypes critical for its function in the heart.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":121655,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9618,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":561636,"name":"Annie M. Westerlund","orcid":"0000-0003-2288-5711","position":1,"is_corresponding":false},{"id":321392,"name":"Jingyi Shi","orcid":"0009-0009-5119-8540","position":2,"is_corresponding":false},{"id":322226,"name":"Kelli McFarland White","orcid":null,"position":3,"is_corresponding":false},{"id":561637,"name":"Alex Dou","orcid":"0000-0001-7446-1676","position":4,"is_corresponding":false},{"id":491048,"name":"Amy H. Cui","orcid":null,"position":5,"is_corresponding":false},{"id":309267,"name":"Jonathan R. Silva","orcid":"0000-0002-3696-3955","position":6,"is_corresponding":false},{"id":561638,"name":"Lucie Delemotte","orcid":"0000-0002-0828-3899","position":7,"is_corresponding":false},{"id":321395,"name":"Jianmin Cui","orcid":"0000-0002-9198-6332","position":8,"is_corresponding":false},{"id":321387,"name":"Po Wei Kang","orcid":"0000-0002-5933-545X","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-18T23:14:46.979435Z","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":[]}