Related Experiment Video

Updated: Jun 14, 2025

Real-time Imaging of Leukotriene B4 Mediated Cell Migration and BLT1 Interactions with β-arrestin
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Structural basis of the cysteinyl leukotriene receptor type 2 activation by LTD4

Mengting Jiang1,2,3, Youwei Xu4, Xiaodong Luan5,6

  • 1Lingang Laboratory, Shanghai 200031, China.

Proceedings of the National Academy of Sciences of the United States of America
|April 7, 2025
PubMed

Insights

Researchers revealed the cryo-electron microscopy structure of the cysteinyl leukotriene receptor 2 (CysLT2R) bound to LTD4. This provides a foundation for developing new drugs targeting CysLT2R for inflammatory diseases and cancer.

Area of Science:

  • Structural Biology
  • Pharmacology
  • Molecular Medicine

Background:

  • The G protein-coupled cysteinyl leukotriene receptor 2 (CysLT2R) is implicated in inflammation, brain injury, CNS disorders, and cancer.
  • CysLT2R is a potential therapeutic target for these conditions.

Purpose of the Study:

  • To determine the cryo-electron microscopy structure of the human CysLT2R in complex with Gαq protein and LTD4.
  • To elucidate the structural basis of CysLT2R activation by LTD4.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was used to determine the structure.
  • The structure was resolved at 3.15 Å resolution.

Main Results:

  • The active conformation of human CysLT2R bound to LTD4 and Gαq protein was determined.
  • A spacious polar pocket accommodating LTD4 and a lateral ligand access route were identified.
  • Transmembrane domain helix 3 was found to be crucial for agonist sensing and receptor activation.

Conclusions:

  • The study provides a structural foundation for understanding CysLT2R activation by LTD4.
  • These findings offer a rational basis for designing novel CysLT2R-targeting therapeutics.
Keywords:
G protein-coupled receptorGαq protein couplingactivation mechanismcryo-electron microscopycysteinyl leukotriene receptor 2

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