9IXX

Structural basis of the cysteinyl leukotriene receptor type 2 activation by LTD4

Summary for 9IXX

• Entry DOI: 10.2210/pdb9ixx/pdb
• EMDB information: 60980
• Descriptor: G-alpha q, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, scFv16, ... (6 entities in total)
• Functional Keywords: gpcr, cyslt2r, ltd4, membrane protein/immune system, membrane protein-immune system complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 153741.82

Authors

Jiang, M.,Xu, Y.,Yin, W. (deposition date: 2024-07-29, release date: 2025-04-02, Last modification date: 2025-04-30)

Primary citation

Jiang, M.,Xu, Y.,Luan, X.,Wu, K.,Li, Z.,Xu, H.E.,Zhang, S.,Jiang, Y.,Yin, W.
Structural basis of the cysteinyl leukotriene receptor type 2 activation by LTD4.
Proc.Natl.Acad.Sci.USA, 122:e2417148122-e2417148122, 2025

PubMed Abstract: The G protein-coupled cysteinyl leukotriene receptor CysLT2R plays intricate roles in the physiology and pathogenesis of inflammation-related processes. It has garnered increasing attention as a potential therapeutic target for atopic asthma, brain injury, central nervous system disorders, and various types of cancer. In this study, we present the cryo-electron microscopy structure of the cysteinyl leukotriene D4 (LTD4)-bound human CysLT2R in complex with a Gα protein, adopting an active conformation at a resolution of 3.15 Å. The structure elucidates a spacious polar pocket designed to accommodate the two branched negative ends of LTD4 and reveals a lateral ligand access route into the orthosteric pocket located on transmembrane domain helix (TM) 4 and 5. Furthermore, our findings highlight the crucial role of transmembrane domain helix 3 in sensing agonist moieties, representing the pivotal mechanism of receptor activation for both CysLT1R and CysLT2R. Collectively, the insights derived from our structural investigation establish a foundation for comprehending CysLT2R activation by its endogenous ligand LTD4, offering a rational basis for the design of drugs targeting CysLT2R.

PubMed: 40193607
DOI: 10.1073/pnas.2417148122

Experimental method

ELECTRON MICROSCOPY (3.15 Å)