{"doi":"10.1101/2022.06.24.497440","title":"Half-calcified Calmodulin Promotes Basal Activity and Inactivation of the Calcium Channel Ca <sub>V</sub> 1.2","abstract":"ABSTRACT The L-type Ca 2+ channel Ca V 1.2 controls gene expression, cardiac contraction, and neuronal activity. Calmodulin (CaM) governs Ca V 1.2 open probability (Po) and Ca 2+ -dependent inactivation (CDI) but the mechanisms remain unclear. We identified a half Ca 2+ -saturated CaM species (Ca 2 /CaM) with Ca 2+ bound solely at the third and fourth EF-hands (EF3 and EF4) under resting Ca 2+ concentrations (50-100 nM) that constitutively pre-associates with Ca V 1.2 to promote Po and CDI. We present an NMR structure of a complex between the Ca V 1.2 IQ motif (residues 1644-1665) and Ca 2 /CaM 12’ , a calmodulin mutant in which Ca 2+ binding to EF1 and EF2 is completely disabled. The CaM 12’ N-lobe does not interact with the IQ motif. The CaM 12’ C-lobe bound two Ca 2+ ions and formed close contacts with IQ residues I1654 and Y1657. I1654A and Y1657D mutations impaired CaM binding, CDI, and Po, as did disabling Ca 2+ binding to EF3 and EF4 in the CaM 34 mutant when compared to wildtype CaM. Accordingly, a previously unappreciated Ca 2 /CaM species promotes Ca V 1.2 Po and CDI identifying Ca 2 /CaM as an important mediator of Ca signaling.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":300227,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"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":923238,"name":"Ian Salveson","orcid":null,"position":1,"is_corresponding":false},{"id":482645,"name":"Andrea M. Coleman","orcid":"0000-0001-7564-8723","position":2,"is_corresponding":false},{"id":421819,"name":"David E. Anderson","orcid":"0000-0001-9334-6438","position":3,"is_corresponding":false},{"id":516859,"name":"Grace Jeng","orcid":null,"position":4,"is_corresponding":false},{"id":519318,"name":"Zoila M. Estrada‐Tobar","orcid":"0000-0002-4212-5325","position":5,"is_corresponding":false},{"id":482647,"name":"Kwun Nok Mimi Man","orcid":"0000-0002-0132-9129","position":6,"is_corresponding":false},{"id":774839,"name":"Qinhong Yu","orcid":"0000-0003-3855-5469","position":7,"is_corresponding":false},{"id":923239,"name":"Elza Kuzmenkina","orcid":null,"position":8,"is_corresponding":false},{"id":316555,"name":"Madeline Nieves‐Cintrón","orcid":"0000-0003-1935-8400","position":9,"is_corresponding":false},{"id":304912,"name":"Manuel F. Navedo","orcid":"0000-0001-6864-6594","position":10,"is_corresponding":false},{"id":482648,"name":"Mary C. Horne","orcid":"0000-0002-2799-3212","position":11,"is_corresponding":false},{"id":355959,"name":"Johannes Hell","orcid":"0000-0001-7960-7531","position":12,"is_corresponding":false},{"id":482649,"name":"James B. Ames","orcid":"0000-0003-0934-2595","position":13,"is_corresponding":false},{"id":355957,"name":"Peter H. Bartels","orcid":"0000-0001-5852-1835","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T00:31:53.559757Z","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":[]}