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Updated: May 4, 2026

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Cryo-EM structure of human lipid phosphate phosphatase 2

Wanyi Wang1, Yue Xu2, Peilin Guo2

  • 1State Key Laboratory of Metabolism and Regulation in Complex Organisms, TaiKang Center for Life and Medical Sciences, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, Hubei 430071, China; Hubei Province Key Laboratory of Allergy and Immunology, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, Hubei 430071, China.

Structure (London, England : 1993)
|May 2, 2026
PubMed

Insights

The study reveals the cryo-EM structure of human lipid phosphate phosphatase-2 (hLPP2), uncovering its tetrameric assembly and broad substrate specificity. This structural insight offers potential for developing new cancer therapies targeting LPP2.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Biology

Background:

  • Lipid phosphate phosphatases (LPPs) regulate cellular signaling and metabolism.
  • LPP2 is implicated in cancer, presenting a potential therapeutic target.
  • The structural and catalytic mechanisms of LPP2 remain largely uncharacterized.

Purpose of the Study:

  • To determine the cryo-electron microscopy (cryo-EM) structure of human LPP2 (hLPP2).
  • To elucidate the molecular mechanisms of hLPP2's structural organization, substrate recognition, and catalysis.
  • To provide insights for the development of targeted cancer therapies.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) for structural determination.
  • Biochemical assays to investigate substrate specificity.
  • Comparative structural analysis with related enzymes.

Main Results:

  • The cryo-EM structure of hLPP2 revealed a homo-tetrameric assembly.
  • Phosphatidylcholine was identified within the substrate pocket, explaining broad substrate specificity.
  • Structural comparisons suggested a conserved catalytic mechanism within the PAP2 family, with E159 playing a key regulatory role.

Conclusions:

  • The tetrameric structure of hLPP2 provides a basis for its oligomerization.
  • The open substrate pocket explains LPP2's broad substrate specificity.
  • Understanding hLPP2 structure and mechanism may facilitate novel cancer therapeutic strategies.
Keywords:
LPP2PAP2 familycryo-EM structurelipid phosphate phosphatase

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