| First Author | Ballesteros A | Year | 2018 |
| Journal | Elife | Volume | 7 |
| PubMed ID | 30063209 | Mgi Jnum | J:269513 |
| Mgi Id | MGI:6269045 | Doi | 10.7554/eLife.38433 |
| Citation | Ballesteros A, et al. (2018) Structural relationship between the putative hair cell mechanotransduction channel TMC1 and TMEM16 proteins. Elife 7:e38433 |
| abstractText | 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. |
