Structural relationship between the putative hair cell mechanotransduction channel TMC1 and TMEM16 proteins
| Autor: | Angela Ballesteros, Cristina Fenollar-Ferrer, Kenton Jon Swartz |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | eLife, Vol 7 (2018) |
| Druh dokumentu: | article |
| ISSN: | 2050-084X 92670156 |
| DOI: | 10.7554/eLife.38433 |
| Popis: | 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. 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. |
| Databáze: | Directory of Open Access Journals |
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