Department of Physiology, University of Texas Southwestern Medical Center, Dallas, United States.
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States.
Elife. 2021 Aug 10;10:e71220. doi: 10.7554/eLife.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.
TMEM120A，也称为 TACAN，是一种在脊椎动物中高度保守的新型膜蛋白，最近被提出是一种参与机械痛觉感知的机械敏感性通道。本文报道了人源 TMEM120A 的单颗粒冷冻电镜（cryo-EM）结构，其通过 N 端卷曲螺旋结构域（CCD）、C 端跨膜结构域（TMD）和两个结构域之间的回折环形成紧密堆积的二聚体，有广泛的相互作用。每个 TMEM120A 亚基的 TMD 包含六个跨膜螺旋（TMs），没有通道蛋白的明确结构特征。相反，这六个 TMs 形成一个 α-桶，其中有一个深口袋，结合了辅酶 A（CoA）分子。有趣的是，尽管它们之间的序列同源性较低，但 TMEM120A 的一些结构特征与非常长链脂肪酸延长酶（ELOVL）相似，这表明 TMEM120A 可能作为脂肪酸代谢的酶，而不是机械敏感性通道发挥作用。
