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Molecular basis of the inositol deacylase PGAP1 involved in quality control of GPI-AP biogenesis

Author

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  • Jingjing Hong

    (Chinese Academy of Sciences; University of Chinese Academy of Sciences)

  • Tingting Li

    (Chinese Academy of Sciences; University of Chinese Academy of Sciences)

  • Yulin Chao

    (Fudan University)

  • Yidan Xu

    (Chinese Academy of Sciences; University of Chinese Academy of Sciences)

  • Zhini Zhu

    (Fudan University)

  • Zixuan Zhou

    (Fudan University)

  • Weijie Gu

    (Chinese Academy of Sciences; University of Chinese Academy of Sciences)

  • Qianhui Qu

    (Fudan University)

  • Dianfan Li

    (Chinese Academy of Sciences; University of Chinese Academy of Sciences)

Abstract

The secretion and quality control of glycosylphosphatidylinositol-anchored proteins (GPI-APs) necessitates post-attachment remodeling initiated by the evolutionarily conserved PGAP1, which deacylates the inositol in nascent GPI-APs. Impairment of PGAP1 activity leads to developmental diseases in humans and fatality and infertility in animals. Here, we present three PGAP1 structures (2.66−2.84 Å), revealing its 10-transmembrane architecture and product-enzyme interaction details. PGAP1 holds GPI-AP acyl chains in an optimally organized, guitar-shaped cavity with apparent energetic penalties from hydrophobic-hydrophilic mismatches. However, abundant glycan-mediated interactions in the lumen counterbalance these repulsions, likely conferring substrate fidelity and preventing off-target hydrolysis of bulk membrane lipids. Structural and biochemical analyses uncover a serine hydrolase-type catalysis with atypical features and imply mechanisms for substrate entrance and product release involving a drawing compass movement of GPI-APs. Our findings advance the mechanistic understanding of GPI-AP remodeling.

Suggested Citation

  • Jingjing Hong & Tingting Li & Yulin Chao & Yidan Xu & Zhini Zhu & Zixuan Zhou & Weijie Gu & Qianhui Qu & Dianfan Li, 2024. "Molecular basis of the inositol deacylase PGAP1 involved in quality control of GPI-AP biogenesis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44568-2
    DOI: 10.1038/s41467-023-44568-2
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    References listed on IDEAS

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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. Yidan Xu & Guowen Jia & Tingting Li & Zixuan Zhou & Yitian Luo & Yulin Chao & Juan Bao & Zhaoming Su & Qianhui Qu & Dianfan Li, 2022. "Molecular insights into biogenesis of glycosylphosphatidylinositol anchor proteins," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. 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.
    4. Yuan Gao & Erhu Cao & David Julius & Yifan Cheng, 2016. "TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action," Nature, Nature, vol. 534(7607), pages 347-351, June.
    5. Yue Fu & David Estoppey & Silvio Roggo & Dominik Pistorius & Florian Fuchs & Christian Studer & Ashraf S. Ibrahim & Thomas Aust & Frederic Grandjean & Manuel Mihalic & Klaus Memmert & Vivian Prindle &, 2020. "Jawsamycin exhibits in vivo antifungal properties by inhibiting Spt14/Gpi3-mediated biosynthesis of glycosylphosphatidylinositol," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    6. Yidan Xu & Tingting Li & Zixuan Zhou & Jingjing Hong & Yulin Chao & Zhini Zhu & Ying Zhang & Qianhui Qu & Dianfan Li, 2023. "Structures of liganded glycosylphosphatidylinositol transamidase illuminate GPI-AP biogenesis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
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