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TitleStructural basis for catalysis of human choline/ethanolamine phosphotransferase 1.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 2529, Year 2023
Publish dateMay 3, 2023
AuthorsZhenhua Wang / Meng Yang / Yufan Yang / Yonglin He / Hongwu Qian /
PubMed AbstractPhosphatidylcholine (PC) and phosphatidylethanolamine (PE) are two primary components of the eukaryotic membrane and play essential roles in the maintenance of membrane integrity, lipid droplet ...Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are two primary components of the eukaryotic membrane and play essential roles in the maintenance of membrane integrity, lipid droplet biogenesis, autophagosome formation, and lipoprotein formation and secretion. Choline/ethanolamine phosphotransferase 1 (CEPT1) catalyzes the last step of the biosynthesis of PC and PE in the Kennedy pathway by transferring the substituted phosphate group from CDP-choline/ethanolamine to diacylglycerol. Here, we present the cryo-EM structures of human CEPT1 and its complex with CDP-choline at resolutions of 3.7 Å and 3.8 Å, respectively. CEPT1 is a dimer with 10 transmembrane segments (TMs) in each protomer. TMs 1-6 constitute a conserved catalytic domain with an interior hydrophobic chamber accommodating a PC-like density. Structural observations and biochemical characterizations suggest that the hydrophobic chamber coordinates the acyl tails during the catalytic process. The PC-like density disappears in the structure of the complex with CDP-choline, suggesting a potential substrate-triggered product release mechanism.
External linksNat Commun / PubMed:37137909 / PubMed Central
MethodsEM (single particle)
Resolution3.7 - 3.9 Å
Structure data

EMDB-34378, PDB-8gyw:
Cryo-EM structure of human CEPT1 complexed with CDP-choline
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-34379, PDB-8gyx:
Cryo-EM structure of human CEPT1
Method: EM (single particle) / Resolution: 3.7 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-CDC:
[2-CYTIDYLATE-O'-PHOSPHONYLOXYL]-ETHYL-TRIMETHYL-AMMONIUM

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM

Source
  • homo sapiens (human)
KeywordsLIPID BINDING PROTEIN / CEPT1 / choline/ethanolamine phosphotransferase

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