{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:54:38Z","timestamp":1790952878880,"version":"4.1.0"},"reference-count":80,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"29","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,7,22]]},"abstract":"<jats:p>\n                    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 (\u201cF-actin\u201d) assembly, which is disrupted by a progressive hearing loss mutation (p.D1647G, \u201c\n                    <jats:italic>jordan<\/jats:italic>\n                    \u201d). Here, we present cryo\u2013electron 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\u2019s D-loop, which mediates inter-subunit contacts, while the\n                    <jats:italic>jordan<\/jats:italic>\n                    mutant locks the D-loop in a single conformation. Adenosine diphosphate\u2013bound 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\u2019s structural plasticity in a myosin nucleotide state\u2013dependent manner. This tunable regulation of actin polymerization could be harnessed to precisely control stereocilium height.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.abl4733","type":"journal-article","created":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T13:57:21Z","timestamp":1658325441000},"source":"Crossref","is-referenced-by-count":56,"title":["Structural basis for tunable control of actin dynamics by myosin-15 in mechanosensory stereocilia"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7270-2974","authenticated-orcid":true,"given":"Rui","family":"Gong","sequence":"first","affiliation":[{"name":"Laboratory of Structural Biophysics and Mechanobiology, The Rockefeller University, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4659-9322","authenticated-orcid":true,"given":"Fangfang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3582-6374","authenticated-orcid":true,"given":"Zane G.","family":"Moreland","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2501-9280","authenticated-orcid":true,"given":"Matthew J.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Laboratory of Structural Biophysics and Mechanobiology, The Rockefeller University, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4510-8296","authenticated-orcid":true,"given":"Santiago Espinosa","family":"de los Reyes","sequence":"additional","affiliation":[{"name":"Laboratory of Structural Biophysics and Mechanobiology, The Rockefeller 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USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7971-445X","authenticated-orcid":true,"given":"Michael R.","family":"Bowl","sequence":"additional","affiliation":[{"name":"Mammalian Genetics Unit, MRC Harwell Institute, Harwell Campus, Oxfordshire, UK."},{"name":"UCL Ear Institute, University College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5531-8794","authenticated-orcid":true,"given":"Jonathan E.","family":"Bird","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7250-4484","authenticated-orcid":true,"given":"Gregory M.","family":"Alushin","sequence":"additional","affiliation":[{"name":"Laboratory of Structural Biophysics and Mechanobiology, The Rockefeller University, New York, 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