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Structural basis for catalysis of human choline/ethanolamine phosphotransferase 1

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  • Zhenhua Wang

    (University of Science and Technology of China)

  • Meng Yang

    (University of Science and Technology of China)

  • Yufan Yang

    (University of Science and Technology of China)

  • Yonglin He

    (University of Science and Technology of China)

  • Hongwu Qian

    (University of Science and Technology of China)

Abstract

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.

Suggested Citation

  • Zhenhua Wang & Meng Yang & Yufan Yang & Yonglin He & Hongwu Qian, 2023. "Structural basis for catalysis of human choline/ethanolamine phosphotransferase 1," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38290-2
    DOI: 10.1038/s41467-023-38290-2
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    1. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. Oliver B. Clarke & David Tomasek & Carla D. Jorge & Meagan Belcher Dufrisne & Minah Kim & Surajit Banerjee & Kanagalaghatta R. Rajashankar & Lawrence Shapiro & Wayne A. Hendrickson & Helena Santos & F, 2015. "Structural basis for phosphatidylinositol-phosphate biosynthesis," Nature Communications, Nature, vol. 6(1), pages 1-11, December.
    3. Przemyslaw Nogly & Ivan Gushchin & Alina Remeeva & Ana M. Esteves & Nuno Borges & Pikyee Ma & Andrii Ishchenko & Sergei Grudinin & Ekaterina Round & Isabel Moraes & Valentin Borshchevskiy & Helena San, 2014. "X-ray structure of a CDP-alcohol phosphatidyltransferase membrane enzyme and insights into its catalytic mechanism," Nature Communications, Nature, vol. 5(1), pages 1-10, September.
    4. Giuliano Sciara & Oliver B. Clarke & David Tomasek & Brian Kloss & Shantelle Tabuso & Rushelle Byfield & Raphael Cohn & Surajit Banerjee & Kanagalaghatta R. Rajashankar & Vesna Slavkovic & Joseph H. G, 2014. "Structural basis for catalysis in a CDP-alcohol phosphotransferase," Nature Communications, Nature, vol. 5(1), pages 1-10, September.
    5. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    6. Martin Centola & Katharina van Pee & Heidi Betz & Özkan Yildiz, 2021. "Crystal structures of phosphatidyl serine synthase PSS reveal the catalytic mechanism of CDP-DAG alcohol O-phosphatidyl transferases," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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