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

• Main Authors: Jing Xue, Yan Han, Hamid Baniasadi, Weizhong Zeng, Jimin Pei, Nick V Grishin, Junmei Wang, Benjamin P Tu, Youxing Jiang
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2021-08-01
• Series: eLife
• Subjects: ion channel; TMEM120A; coenzyme a
• Online Access: https://elifesciences.org/articles/71220

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.