{"doi":"10.1038/s42003-024-06265-8","title":"Fast myosin binding protein C knockout in skeletal muscle alters length-dependent activation and myofilament structure","abstract":"Abstract In striated muscle, the sarcomeric protein myosin-binding protein-C (MyBP-C) is bound to the myosin thick filament and is predicted to stabilize myosin heads in a docked position against the thick filament, which limits crossbridge formation. Here, we use the homozygous Mybpc2 knockout (C2 -/- ) mouse line to remove the fast-isoform MyBP-C from fast skeletal muscle and then conduct mechanical functional studies in parallel with small-angle X-ray diffraction to evaluate the myofilament structure. We report that C2 −/− fibers present deficits in force production and calcium sensitivity. Structurally, passive C2 -/- fibers present altered sarcomere length-independent and -dependent regulation of myosin head conformations, with a shift of myosin heads towards actin. At shorter sarcomere lengths, the thin filament is axially extended in C2 -/- , which we hypothesize is due to increased numbers of low-level crossbridges. These findings provide testable mechanisms to explain the etiology of debilitating diseases associated with MyBP-C.","journal":"Communications Biology","year":2024,"id":459572,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9595,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1165443,"name":"Michel N. Kuehn","orcid":"0000-0001-7232-2517","position":1,"is_corresponding":false},{"id":1194107,"name":"Seong-won Han","orcid":"0000-0003-1711-658X","position":2,"is_corresponding":false},{"id":355530,"name":"Weikang Ma","orcid":"0000-0001-9535-7114","position":3,"is_corresponding":false},{"id":355536,"name":"Thomas C. Irving","orcid":"0000-0003-4848-3323","position":4,"is_corresponding":false},{"id":1194108,"name":"Brent A. Momb","orcid":"0000-0002-9171-0272","position":5,"is_corresponding":false},{"id":274728,"name":"Taejeong Song","orcid":"0000-0001-6648-1263","position":6,"is_corresponding":false},{"id":274731,"name":"Sakthivel Sadayappan","orcid":"0000-0003-2006-7678","position":7,"is_corresponding":false},{"id":318287,"name":"Wolfgang A. Linke","orcid":"0000-0003-0801-3773","position":8,"is_corresponding":false},{"id":369666,"name":"Bradley M. Palmer","orcid":"0000-0002-4388-3160","position":9,"is_corresponding":false},{"id":683316,"name":"Anthony L. Hessel","orcid":"0000-0003-4278-4221","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:03:59.428859Z","pmid":"38802450","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":[]}