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bioRxiv · 10.1101/2021.06.13.448233

TMEM120 is a coenzyme A-binding membrane protein with structural similarities to ELOVL fatty acid elongase

Xue, J.·Han, Y.·Baniasadi, H.·Zeng, W.·Pei, J.·Grishin, N.·Wang, J.·Tu, B. P.·Jiang, Y.
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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 -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 TEME120A may function as an enzyme for fatty acid metabolism, rather than a mechanosensitive channel.

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Xue, J., Han, Y., Baniasadi, H., Zeng, W., Pei, J., Grishin, N., Wang, J., Tu, B. P., Jiang, Y.. 2021-06-13. TMEM120 is a coenzyme A-binding membrane protein with structural similarities to ELOVL fatty acid elongase. https://doi.org/10.1101/2021.06.13.448233

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