TMEM120A is a coenzyme A-binding membrane protein with structural similarities to ELOVL fatty acid elongase
- University of Texas Southwestern Medical Center, United States
- 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
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Cryo-EM structure of human TMEM120AElectron Microscopy Data Bank, EMD-24230.
Article and author information
Author details
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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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
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