{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:54:52Z","timestamp":1790229292435,"version":"4.1.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"24","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"HHS | NIH | National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["DC005965"],"award-info":[{"award-number":["DC005965"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM154904"],"award-info":[{"award-number":["GM154904"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM157915"],"award-info":[{"award-number":["GM157915"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"HHS | NIH | National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["DC023325"],"award-info":[{"award-number":["DC023325"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,6,16]]},"abstract":"<jats:p>Tip links connect the stereocilia of mechanosensory hair cells in the inner ear and transmit force onto mechanotransduction (MET) channels. Tip links consist of protocadherin 15 (PCDH15) and cadherin 23, which assemble into an extracellular filament approximately 150 nm in length. Rare freeze-etched electron microscopy (EM) images have suggested that tip links could be right-handed double helices in vivo, but direct structural evidence has been lacking. Using cryo-EM we determined the structure of a large part of the extracellular PCDH15 domain. Two PCDH15 molecules form a parallel cis dimer stabilized by several dimerization interfaces, including two strand crossovers and two parallel contacts, yielding a right-handed double helix. Functional studies show that mutations in PCDH15 dimerization-domains impair MET. Our results establish the molecular foundation for how PCDH15 forms a right-handed double helix to enable mechanical sensing.<\/jats:p>","DOI":"10.1073\/pnas.2607573123","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T17:36:04Z","timestamp":1781026564000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Cryo-EM reveals a right-handed double-helix dimer architecture of PCDH15"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4542-8814","authenticated-orcid":false,"given":"Xiaoping","family":"Liang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9983-5491","authenticated-orcid":false,"given":"Roshan","family":"Pathak","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xufeng","family":"Qiu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Dillard","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1855-1586","authenticated-orcid":false,"given":"Edward C.","family":"Twomey","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2736-6494","authenticated-orcid":false,"given":"Ulrich","family":"M\u00fcller","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine","place":["Baltimore"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2017.tb00783.x"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.09.018"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06091"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/321277"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.16.1709"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/83667"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/316954"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/83660"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13458"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1920444117"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2018.11.010"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.07.006"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006284107"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2018.06.003"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.7b01075"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2017.01.014"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.03.028"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11590"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071559"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1784"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.12.046"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902163116"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.38770"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.24.13336"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","unstructured":"X. Liang L. Dillard R. Pathak E. C. Twomey U. M\u00fcller Data from \u201cProtocadherin-15 extracellular domains 1-7.\u201d EMBD. https:\/\/www.ebi.ac.uk\/emdb\/EMD-75730. Deposited 26 February 2026.","DOI":"10.2210\/pdb11iy\/pdb"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900691106"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201403976"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.060061"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.10.041"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.168"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.10.041"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1163-06.2006"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22456"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4251-05.2006"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4169"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4347"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3943"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798318002425"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904019158"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798319011471"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.01456"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3330"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.03.033"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.05.007"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112245"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2607573123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T17:36:26Z","timestamp":1781026586000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2607573123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":47,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2026,6,16]]}},"alternative-id":["10.1073\/pnas.2607573123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2607573123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,9]]},"assertion":[{"value":"2026-03-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2607573123"}}