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Structure of a eukaryotic cholinephosphotransferase-1 reveals mechanisms of substrate recognition and catalysis

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  • Lie Wang

    (Baylor College of Medicine)

  • Ming Zhou

    (Baylor College of Medicine)

Abstract

Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic cell membranes. In eukaryotes, two highly homologous enzymes, cholinephosphotransferase-1 (CHPT1) and choline/ethanolamine phosphotransferase-1 (CEPT1) catalyze the final step of de novo PC synthesis. CHPT1/CEPT1 joins two substrates, cytidine diphosphate-choline (CDP-choline) and diacylglycerol (DAG), to produce PC, and Mg2+ is required for the reaction. However, mechanisms of substrate recognition and catalysis remain unresolved. Here we report structures of a CHPT1 from Xenopus laevis (xlCHPT1) determined by cryo-electron microscopy to an overall resolution of ~3.2 Å. xlCHPT1 forms a homodimer, and each protomer has 10 transmembrane helices (TMs). The first 6 TMs carve out a cone-shaped enclosure in the membrane in which the catalysis occurs. The enclosure opens to the cytosolic side, where a CDP-choline and two Mg2+ are coordinated. The structures identify a catalytic site unique to eukaryotic CHPT1/CEPT1 and suggest an entryway for DAG. The structures also reveal an internal pseudo two-fold symmetry between TM3-6 and TM7-10, and suggest that CHPT1/CEPT1 may have evolved from their distant prokaryotic ancestors through gene duplication.

Suggested Citation

  • Lie Wang & Ming Zhou, 2023. "Structure of a eukaryotic cholinephosphotransferase-1 reveals mechanisms of substrate recognition and catalysis," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38003-9
    DOI: 10.1038/s41467-023-38003-9
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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. Lie Wang & Hongwu Qian & Yin Nian & Yimo Han & Zhenning Ren & Hanzhi Zhang & Liya Hu & B. V. Venkataram Prasad & Arthur Laganowsky & Nieng Yan & Ming Zhou, 2020. "Structure and mechanism of human diacylglycerol O-acyltransferase 1," Nature, Nature, vol. 581(7808), pages 329-332, May.
    5. Lie Wang & Kehan Chen & Ming Zhou, 2021. "Structure and function of an Arabidopsis thaliana sulfate transporter," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    6. 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.
    7. Yonghong Bai & Jason G. McCoy & Elena J. Levin & Pablo Sobrado & Kanagalaghatta R. Rajashankar & Brian G. Fox & Ming Zhou, 2015. "X-ray structure of a mammalian stearoyl-CoA desaturase," Nature, Nature, vol. 524(7564), pages 252-256, August.
    8. 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.
    9. 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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