Molecular insights into ago-allosteric modulation at cysteinyl leukotriene receptor 2.

ABSTRACT: Cysteinyl leukotriene receptor CysLT2R, which is activated by the endogenous cysteinyl leukotrienes (CysLTs) LTC4, LTD4, and LTE4, has emerged as a potential therapeutic target due to the involvement in various inflammatory diseases. Accumulating evidence indicates that CysLT2R is also involved in the pathogenesis of cardiovascular diseases and contribute to tumor progression in cancer. However, the structural basis underlying the ligand recognition and the receptor activation remains to be elucidated. Here, we present two cryo-electron microscopy (cryo-EM) structures of the human CysLT2R-G_q complexes bound to LTC4 and LTD4. CysLTs are characterized as ago-allosteric modulators (ago-PAMs) of CysLT2R. Our structures reveal that CysLTs are recognized by a lipid-facing pocket above

SUBMITTER: Li M 

PROVIDER: S-EPMC12830604 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature