bioRxiv preprint doi: https://doi.org/10.1101/327072; this version posted May 21, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 05/16/2018 Structural relationship between the putative hair cell mechanotransduction channel TMC1 and TMEM16 proteins Angela Ballesteros1, Cristina Fenollar-Ferrer2 and Kenton J. Swartz1. 1 Molecular Physiology and Biophysics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. 2 Laboratory of Molecular & Cellular Neurobiology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892. Correspondence to: Kenton Swartz (
[email protected]) Key words structural biology, membrane protein structure, ion channel pore, deafness mutations, Ca2+- activated Cl- channel, lipid scramblase 1 bioRxiv preprint doi: https://doi.org/10.1101/327072; this version posted May 21, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Abstract The hair cell mechanotransduction (MET) channel complex is essential for hearing, yet it’s molecular identity and structure remain elusive. The transmembrane channel–like 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.