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TitleTMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells.
Journal, issue, pagesElife, Vol. 10, Year 2021
Publish dateAug 19, 2021
AuthorsYao Rong / Jinghui Jiang / Yiwei Gao / Jianli Guo / Danfeng Song / Wenhao Liu / Mingmin Zhang / Yan Zhao / Bailong Xiao / Zhenfeng Liu /
PubMed AbstractTMEM120A, 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 ...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 (TMEM120A) in complex with an endogenous metabolic cofactor (coenzyme A, CoASH) and in the apo form. TMEM120A 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 TMEM120A with CoASH. TMEM120A 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.
External linksElife / PubMed:34409941 / PubMed Central
MethodsEM (single particle)
Resolution3.69 - 4.0 Å
Structure data

EMDB-31440, PDB-7f3t:
Cryo-EM structure of human TMEM120A in the CoASH-bound state
Method: EM (single particle) / Resolution: 3.69 Å

EMDB-31441, PDB-7f3u:
Cryo-EM structure of human TMEM120A in the CoASH-free state
Method: EM (single particle) / Resolution: 4.0 Å

Chemicals

ChemComp-COA:
COENZYME A / Coenzyme A

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Human / COA

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