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

  1. Jing Xue
  2. Yan Han
  3. Hamid Baniasadi
  4. Weizhong Zeng
  5. Jimin Pei
  6. Nick V Grishin
  7. Junmei Wang
  8. Benjamin P Tu
  9. Youxing Jiang  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States
  2. University of Pittsburgh, United States

Abstract

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 cryo-EM structure of human TMEM120A which forms a tightly packed dimer with extensive interactions mediate 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 acid (ELOVL) despite 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.

Data availability

The cryo-EM density map and the atomic coordinates of the human TMEM120A have been deposited in the Electron Microscopy Data Bank under accession numbers EMD-24230 and the Protein Data Bank under accession numbers 7N7P, respectively

The following data sets were generated

Article and author information

Author details

  1. Jing Xue

    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7331-1382
  2. Yan Han

    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Hamid Baniasadi

    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Weizhong Zeng

    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jimin Pei

    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Nick V Grishin

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Junmei Wang

    University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Benjamin P Tu

    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5545-9183
  9. Youxing Jiang

    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    youxing.jiang@utsouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1874-0504

Funding

Howard Hughes Medical Institute

  • Youxing Jiang

Howard Hughes Medical Institute

  • Nick V Grishin

National Institute of General Medical Sciences (R35GM140892)

  • Youxing Jiang

National Institute of General Medical Sciences (R35GM136370)

  • Benjamin P Tu

National Institute of General Medical Sciences (GM127390)

  • Nick V Grishin

Welch Foundation (I-1578)

  • Youxing Jiang

Welch Foundation (I-1505)

  • Nick V Grishin

National Science Foundation (1955260)

  • Junmei Wang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2021, Xue 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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  1. Jing Xue
  2. Yan Han
  3. Hamid Baniasadi
  4. Weizhong Zeng
  5. Jimin Pei
  6. Nick V Grishin
  7. Junmei Wang
  8. Benjamin P Tu
  9. Youxing Jiang
(2021)
TMEM120A is a coenzyme A-binding membrane protein with structural similarities to ELOVL fatty acid elongase
eLife 10:e71220.
https://doi.org/10.7554/eLife.71220

Share this article

https://doi.org/10.7554/eLife.71220

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