{"doi":"10.1126/sciadv.abl4733","title":"Structural basis for tunable control of actin dynamics by myosin-15 in mechanosensory stereocilia","abstract":"The motor protein myosin-15 is necessary for the development and maintenance of mechanosensory stereocilia, and mutations in myosin-15 cause hereditary deafness. In addition to transporting actin regulatory machinery to stereocilia tips, myosin-15 directly nucleates actin filament (“F-actin”) assembly, which is disrupted by a progressive hearing loss mutation (p.D1647G, “ jordan ”). Here, we present cryo–electron microscopy structures of myosin-15 bound to F-actin, providing a framework for interpreting the impacts of deafness mutations on motor activity and actin nucleation. Rigor myosin-15 evokes conformational changes in F-actin yet maintains flexibility in actin’s D-loop, which mediates inter-subunit contacts, while the jordan mutant locks the D-loop in a single conformation. Adenosine diphosphate–bound myosin-15 also locks the D-loop, which correspondingly blunts actin-polymerization stimulation. We propose myosin-15 enhances polymerization by bridging actin protomers, regulating nucleation efficiency by modulating actin’s structural plasticity in a myosin nucleotide state–dependent manner. This tunable regulation of actin polymerization could be harnessed to precisely control stereocilium height.","journal":"Science Advances","year":2022,"id":237969,"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":57,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"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":412611,"name":"Fangfang Jiang","orcid":null,"position":1,"is_corresponding":false},{"id":806945,"name":"Zane G. Moreland","orcid":"0000-0003-3582-6374","position":2,"is_corresponding":false},{"id":279311,"name":"Matthew J. Reynolds","orcid":"0000-0002-2501-9280","position":3,"is_corresponding":false},{"id":255382,"name":"Santiago Espinosa de los Reyes","orcid":"0000-0003-4510-8296","position":4,"is_corresponding":false},{"id":860968,"name":"Pinar S. Gurel","orcid":"0000-0003-1956-2591","position":5,"is_corresponding":false},{"id":411444,"name":"Arik Shams","orcid":"0000-0002-0151-0593","position":6,"is_corresponding":false},{"id":734201,"name":"James B. Heidings","orcid":"0000-0001-7358-1705","position":7,"is_corresponding":false},{"id":457064,"name":"Michael R. Bowl","orcid":"0000-0001-7971-445X","position":8,"is_corresponding":false},{"id":304021,"name":"Jonathan E. Bird","orcid":"0000-0001-5531-8794","position":9,"is_corresponding":false},{"id":255384,"name":"Gregory M. Alushin","orcid":"0000-0001-7250-4484","position":10,"is_corresponding":false},{"id":255381,"name":"Rui Gong","orcid":"0000-0001-7270-2974","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T00:22:21.693802Z","pmid":"35857845","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":[]}