{"doi":"10.1085/jgp.202513838","title":"Resolving zone-specific regulation of cardiac myosin","abstract":"Cardiac contractility is driven by shortening of ∼2-μm-long, macromolecular assemblies known as sarcomeres. During contraction, the motor protein myosin binds to, and exerts force upon actin filaments, utilizing energy from the hydrolysis of ATP. When not actively contracting, myosin partition into two subpopulations, distinguished by their basal rates of ATP hydrolysis, known as the \"Disordered Relaxed\" (DRX) and \"Super Relaxed\" (SRX) states. Additionally, the slower hydrolyzing SRX state has been proposed as a sequestered or \"reserve pool\" of myosin that do not contribute to contraction but can be recruited for enhanced contractility in response to external stimuli. Thus, the fraction of myosin in the SRX state is thought to reflect the overall regulatory state of the myosin population. In this volume of the Journal of General Physiology, a study by Pilagov et al. explores how the SRX state is regulated by phosphorylation or haploinsufficiency of a key regulatory protein, Myosin Binding Protein-C (MyBP-C). Surprisingly, they found that perturbations of MyBP-C led to a negligible change in the overall abundance of SRX. Instead, they found a rearrangement of SRX myosin throughout the sarcomere - specifically a decrease in SRX in regions of the sarcomere that contain MyBP-C and a compensatory increase in SRX in regions lacking MyBP-C. Their findings suggest that the influence of MyBP-C extends beyond its immediate vicinity and can simultaneously exert both positive and negative effects in a location-specific manner.","journal":"The Journal of General Physiology","year":2025,"id":573577,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9457,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":347182,"name":"Shane R. Nelson","orcid":"0000-0002-3032-6314","position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":null,"created_at":"2026-07-19T02:57:36.753600Z","pmid":"40876855","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":[]}