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U.S.A."],"published-print":{"date-parts":[[2020,10,6]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>When sound vibrations reach the inner ear, fine protein filaments called \u201ctip links\u201d stretch and open cochlear hair-cell mechanosensitive channels that trigger sensory perception. Similarly, vestibular hair cells use tip links to sense mechanical stimuli produced by head motions. Tip links are formed by cadherin-23 and protocadherin-15, two large proteins involved in hearing loss and balance disorders. Here we present multiple structures, models, and simulations that depict the lower end of the tip link, including the complete protocadherin-15 ectodomain. These models show an essential connection between cadherin-23 and protocadherin-15 with dual molecular \u201chandshakes\u201d and various protein sites that are mutated in inherited deafness. The simulations also reveal how the tip link responds to force to mediate hearing and balance sensing.<\/jats:p>","DOI":"10.1073\/pnas.1920444117","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T17:01:29Z","timestamp":1600794089000},"page":"24837-24848","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":53,"title":["Structural determinants of protocadherin-15 mechanics and function in hearing and balance perception"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2912-1610","authenticated-orcid":false,"given":"Deepanshu","family":"Choudhary","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1136-282X","authenticated-orcid":false,"given":"Yoshie","family":"Narui","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5983-9335","authenticated-orcid":false,"given":"Brandon L.","family":"Neel","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210;"},{"name":"The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8611-0192","authenticated-orcid":false,"given":"Lahiru N.","family":"Wimalasena","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5277-1315","authenticated-orcid":false,"given":"Carissa F.","family":"Klanseck","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2434-3345","authenticated-orcid":false,"given":"Pedro","family":"De-la-Torre","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5305-1707","authenticated-orcid":false,"given":"Conghui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4872-3553","authenticated-orcid":false,"given":"Raul","family":"Araya-Secchi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210;"},{"name":"Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2347-6805","authenticated-orcid":false,"given":"Elakkiya","family":"Tamilselvan","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210;"},{"name":"Biophysics Program, The Ohio State University, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3333-1805","authenticated-orcid":false,"given":"Marcos","family":"Sotomayor","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210;"},{"name":"The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210;"},{"name":"Biophysics Program, The Ohio State University, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,9,22]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00038.2013"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3786"},{"key":"e_1_3_4_3_2","first-page":"75","volume-title":"Mechanical Transduction Processes in the Hair Cell","author":"Corey D. P.","year":"2017","unstructured":"D. P. Corey, D. \u00d3 Maoil\u00e9idigh, J. F. Ashmore, Mechanical Transduction Processes in the Hair Cell (Springer, Cham, 2017), pp. 75\u2013111."},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(84)90041-8"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90343-X"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.24.13336"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.16041"},{"key":"e_1_3_4_8_2","first-page":"1721","article-title":"The composition and role of cross links in mechanoelectrical transduction in vertebrate sensory hair cells","volume":"126","author":"Hackney C. M.","year":"2013","unstructured":"C. M. Hackney, D. N. Furness, The composition and role of cross links in mechanoelectrical transduction in vertebrate sensory hair cells. J. Cell Sci. 126, 1721\u20131731 (2013).","journal-title":"J. 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