TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells

eLife

Jianli Guo¹  Zhenfeng Liu²  Danfeng Song²  Yiwei Gao²  Yao Rong²  Yan Zhao³  Bailong Xiao⁴  Jinghui Jiang⁴  Mingmin Zhang⁴  Wenhao Liu⁴ 

[1] National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China;National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China;State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;State Key Laboratory of Membrane Biology; Tsinghua-Peking Center for Life Sciences; Beijing Advanced Innovation Center for Structural Biology; IDG/McGovern Institute for Brain Research; School of Pharmaceutical Sciences, Tsinghua University, Beijing, China;

关键词: TMEM120;    coenzyme A;    membrane protein;    mechanosensation;    ion channel;    cryo-EM structure;    Human;    Mouse;   

DOI  :  10.7554/eLife.71474

来源: eLife Sciences Publications, Ltd

【 摘 要 】

TMEM120A, a member of the transmembrane protein 120 (TMEM120) family, has a pivotal function in adipocyte differentiation and metabolism, and may also contribute to sensing mechanical pain by functioning as an ion channel named TACAN. Here we report that expression of TMEM120A is not sufficient in mediating poking- or stretch-induced currents in cells and have solved cryo-electron microscopy (cryo-EM) structures of human TMEM120A (HsTMEM120A) in complex with an endogenous metabolic cofactor (coenzyme A, CoASH) and in the apo form. HsTMEM120A forms a symmetrical homodimer with each monomer containing an amino-terminal coiled-coil motif followed by a transmembrane domain with six membrane-spanning helices. Within the transmembrane domain, a CoASH molecule is hosted in a deep cavity and forms specific interactions with nearby amino acid residues. Mutation of a central tryptophan residue involved in binding CoASH dramatically reduced the binding affinity of HsTMEM120A with CoASH. HsTMEM120A exhibits distinct conformations at the states with or without CoASH bound. Our results suggest that TMEM120A may have alternative functional roles potentially involved in CoASH transport, sensing, or metabolism.

【 授权许可】

CC BY