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Structure and mechanism of an intramembrane liponucleotide synthetase central for phospholipid biosynthesis

Author

Listed:
  • Xiuying Liu

    (National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences)

  • Yan Yin

    (National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Jinjun Wu

    (National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences)

  • Zhenfeng Liu

    (National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences)

Abstract

Phospholipids are elemental building-block molecules for biological membranes. Biosynthesis of phosphatidylinositol, phosphatidylglycerol and phosphatidylserine requires a central liponucleotide intermediate named cytidine-diphosphate diacylglycerol (CDP-DAG). The CDP-DAG synthetase (Cds) is an integral membrane enzyme catalysing the formation of CDP-DAG, an essential step for phosphoinositide recycling during signal transduction. Here we report the structure of the Cds from Thermotoga maritima (TmCdsA) at 3.4 Å resolution. TmCdsA forms a homodimer and each monomer contains nine transmembrane helices arranged into a novel fold with three domains. An unusual funnel-shaped cavity penetrates half way into the membrane, allowing the enzyme to simultaneously accept hydrophilic substrate (cytidine 5′-triphosphate (CTP)/deoxy-CTP) from cytoplasm and hydrophobic substrate (phosphatidic acid) from membrane. Located at the bottom of the cavity, a Mg2+-K+ hetero-di-metal centre coordinated by an Asp-Asp dyad serves as the cofactor of TmCdsA. The results suggest a two-metal-ion catalytic mechanism for the Cds-mediated synthesis of CDP-DAG at the membrane–cytoplasm interface.

Suggested Citation

  • Xiuying Liu & Yan Yin & Jinjun Wu & Zhenfeng Liu, 2014. "Structure and mechanism of an intramembrane liponucleotide synthetase central for phospholipid biosynthesis," Nature Communications, Nature, vol. 5(1), pages 1-10, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5244
    DOI: 10.1038/ncomms5244
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