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Structural relationship between the putative hair cell mechanotransduction channel TMC1 and TMEM16 proteins
- Source :
- eLife, Vol 7 (2018)
- Publication Year :
- 2018
- Publisher :
- eLife Sciences Publications Ltd, 2018.
-
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. 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.
Details
- Language :
- English
- ISSN :
- 2050084X and 92670156
- Volume :
- 7
- Database :
- Directory of Open Access Journals
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.11ac926701564aee8284ed73eb1ab5e5
- Document Type :
- article
- Full Text :
- https://doi.org/10.7554/eLife.38433