1. Structural Biology and Molecular Biophysics

Analysis of the Mechanosensor Channel Functionality of TACAN

  1. Yiming Niu
  2. Xiao Tao
  3. George Vaisey
  4. Paul D B Olinares
  5. Hanan Alwaseem
  6. Brian Chait
  7. Roderick MacKinnon  Is a corresponding author
  1. Howard Hughes Medical Institute, The Rockefeller University, United States
  2. Rockefeller University, United States
  3. The Rockefeller University, United States
https://doi.org/10.7554/eLife.71188
Share this article
Cite this article
  1. Yiming Niu
  2. Xiao Tao
  3. George Vaisey
  4. Paul D B Olinares
  5. Hanan Alwaseem
  6. Brian Chait
  7. Roderick MacKinnon
(2021)
Analysis of the Mechanosensor Channel Functionality of TACAN
eLife 10:e71188.
https://doi.org/10.7554/eLife.71188
  2. Download BibTeX
  3. Download .RIS

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.

The following data sets were generated

Article and author information

Author details

  1. Yiming Niu

    Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5683-1781

  2. Xiao Tao

    Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9381-7903

  3. George Vaisey

    Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Paul D B Olinares

    Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3429-6618

  5. Hanan Alwaseem

    Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Brian Chait

    Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Roderick MacKinnon

    Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York, United States
    For correspondence
    mackinn@mail.rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7605-4679

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.

Metrics

  • 2,857
    views
  • 394
    downloads
  • 27
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Citations by DOI

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Yiming Niu
  2. Xiao Tao
  3. George Vaisey
  4. Paul D B Olinares
  5. Hanan Alwaseem
  6. Brian Chait
  7. Roderick MacKinnon
(2021)
Analysis of the Mechanosensor Channel Functionality of TACAN
eLife 10:e71188.
https://doi.org/10.7554/eLife.71188

Share this article

https://doi.org/10.7554/eLife.71188

Categories and tags

Research organisms

Further reading

    1. Structural Biology and Molecular Biophysics

    TMEM120A is a coenzyme A-binding membrane protein with structural similarities to ELOVL fatty acid elongase

    Jing Xue, Yan Han ... Youxing Jiang
    Research Article Updated

    TMEM120A, also named as TACAN, is a novel membrane protein highly conserved in vertebrates and was recently proposed to be a mechanosensitive channel involved in sensing mechanical pain. Here we present the single-particle cryogenic electron microscopy (cryo-EM) structure of human TMEM120A, which forms a tightly packed dimer with extensive interactions mediated by the N-terminal coiled coil domain (CCD), the C-terminal transmembrane domain (TMD), and the re-entrant loop between the two domains. The TMD of each TMEM120A subunit contains six transmembrane helices (TMs) and has no clear structural feature of a channel protein. Instead, the six TMs form an α-barrel with a deep pocket where a coenzyme A (CoA) molecule is bound. Intriguingly, some structural features of TMEM120A resemble those of elongase for very long-chain fatty acids (ELOVL) despite the low sequence homology between them, pointing to the possibility that TMEM120A may function as an enzyme for fatty acid metabolism, rather than a mechanosensitive channel.