RT Journal Article
SR Electronic
T1 TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.17.448797
DO 10.1101/2021.06.17.448797
A1 Yao Rong
A1 Jinghui Jiang
A1 Yiwei Gao
A1 Jianli Guo
A1 Danfeng Song
A1 Wenhao Liu
A1 Yan Zhao
A1 Bailong Xiao
A1 Zhenfeng Liu
YR 2021
UL http://biorxiv.org/content/early/2021/06/17/2021.06.17.448797.abstract
AB TMEM120A, a member of the Transmembrane protein 120 (TMEM120) family, has 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-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.Competing Interest StatementThe authors have declared no competing interest.