Analysis of the Mechanosensor Channel Functionality of TACAN
- Howard Hughes Medical Institute, The Rockefeller University, United States
- Rockefeller University, United States
- The Rockefeller University, United States
Abstract
Mechanosensitive ion channels mediate transmembrane ion currents activated by mechanical forces. A mechanosensitive ion channel called TACAN was recently reported. We began to study TACAN with the intent to understand how it senses mechanical forces and functions as an ion channel. Using cellular patch-recording methods we failed to identify mechanosensitive ion channel activity. Using membrane reconstitution methods we found that TACAN, at high protein concentrations, produces heterogeneous conduction levels that are not mechanosensitive and are most consistent with disruptions of the lipid bilayer. We determined the structure of TACAN using single particle cryo-EM and observe that it forms a symmetrical dimeric transmembrane protein. Each protomer contains an intracellular-facing cleft with a coenzyme-A cofactor, confirmed by mass spectrometry. The TACAN protomers are related in 3-dimensional structure to a fatty acid elongase, ELOVL. Whilst its physiological function remains unclear, we anticipate that TACAN is not a mechanosensitive ion channel.
Data availability
The B-factor sharpened 3D cryo-EM density map and atomic coordinates of wild-type TACAN have been deposited in Worldwide Protein Data Bank (wwPDB) under accession codes 7N0K and EMD-24107.The B-factor sharpened 3D cryo-EM density map and atomic coordinates of His196Ala, His197Ala mutant TACAN have been deposited in Worldwide Protein Data Bank (wwPDB) under accession codes 7N0L and EMD-24108.
Article and author information
Author details
Roderick MacKinnon
Funding
National Institutes of Health (GM43949)
- Roderick MacKinnon
National Institutes of Health (GM109824)
- Brian Chait
National Institutes of Health (GM103314)
- Brian Chait
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Niu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Analysis of the Mechanosensor Channel Functionality of TACAN
eLife 10:e71188.
https://doi.org/10.7554/eLife.71188
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