EMD-31440

Single-particle
3.69 Å
EMD-31440 Deposition: 17/06/2021
Map released: 30/06/2021
Last modified: 12/06/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-31440

Cryo-EM structure of human TMEM120A in the CoASH-bound state

EMD-31440

Single-particle
3.69 Å
EMD-31440 Deposition: 17/06/2021
Map released: 30/06/2021
Last modified: 12/06/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: transmembrane protein 120A
Fitted models: 7f3t (Avg. Q-score: 0.443)

Deposition Authors: Song DF, Rong Y
TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells.
Rong Y , Jiang J, Gao Y , Guo J, Song D, Liu W, Zhang M, Zhao Y, Xiao B, Liu Z
(2021) eLife , 10
PUBMED: 34409941
DOI: doi:10.7554/eLife.71474
ISSN: 2050-084X
Abstract:
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.