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The transmembrane channel\u2013like 1 (TMC1) protein localizes to the site of the MET channel, interacts with the tip-link responsible for mechanical gating, and genetic alterations in TMC1 alter MET channel properties and cause deafness, supporting the hypothesis that TMC1 forms the MET channel. We generated a model of TMC1 based on X-ray and cryo-EM structures of TMEM16 proteins, revealing the presence of a large cavity near the protein-lipid interface that also harbors the Beethoven mutation, suggesting that it could function as a permeation pathway. We also find that hair cells are permeable to 3 kDa dextrans, and that dextran permeation requires TMC1\/2 proteins and functional MET channels, supporting the presence of a large permeation pathway and the hypothesis that TMC1 is a pore forming subunit of the MET channel complex.<\/jats:p>","DOI":"10.7554\/elife.38433","type":"journal-article","created":{"date-parts":[[2018,7,31]],"date-time":"2018-07-31T09:00:20Z","timestamp":1533027620000},"source":"Crossref","is-referenced-by-count":122,"title":["Structural relationship between the putative hair cell mechanotransduction channel TMC1 and TMEM16 proteins"],"prefix":"10.7554","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5796-6875","authenticated-orcid":true,"given":"Angela","family":"Ballesteros","sequence":"first","affiliation":[{"name":"Molecular Physiology and Biophysics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Fenollar-Ferrer","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular & Cellular Neurobiology, National Institute of Mental Health, National Institutes of Health, Bethesda, United States"},{"name":"Laboratory of Molecular Genetics, National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States"},{"name":"Molecular Biology and Genetics Section, National Institute of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3419-0765","authenticated-orcid":true,"given":"Kenton Jon","family":"Swartz","sequence":"additional","affiliation":[{"name":"Molecular Physiology and Biophysics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, 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