9J5V
Human Lysophosphatidic Acid Receptor 1-Gi complex bound to CpY
This is a non-PDB format compatible entry.
Summary for 9J5V
| Entry DOI | 10.2210/pdb9j5v/pdb |
| EMDB information | 61154 |
| Descriptor | Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, Guanine nucleotide-binding protein G(i) subunit alpha-1, ... (6 entities in total) |
| Functional Keywords | gpcr, membrane protein |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 5 |
| Total formula weight | 178994.00 |
| Authors | Akasaka, H.,Shihoya, W.,Nureki, O. (deposition date: 2024-08-13, release date: 2024-11-27, Last modification date: 2025-07-02) |
| Primary citation | Akasaka, H.,Sano, F.K.,Shihoya, W.,Nureki, O. Structural mechanisms of potent lysophosphatidic acid receptor 1 activation by nonlipid basic agonists. Commun Biol, 7:1444-1444, 2024 Cited by PubMed Abstract: Lysophosphatidic acid receptor 1 (LPA) is one of the G protein-coupled receptors activated by the lipid mediator, lysophosphatidic acid (LPA). LPA is associated with a variety of diseases, and LPA agonists have potential therapeutic value for treating obesity and depression. Although potent nonlipid LPA agonists have recently been identified, the mechanisms of nonlipid molecule-mediated LPA activation remain unclear. Here, we report a cryo-electron microscopy structure of the human LPA-G complex bound to a nonlipid basic agonist, CpY, which has 30-fold higher agonistic activity as compared with LPA. Structural comparisons of LPA with other lipid GPCRs revealed that the negative charge in the characteristic binding pocket of LPA allows the selective recognition of CpY, which lacks a polar head. In addition, our structure show that the ethyl group of CpY directly pushes W271 to fix the active conformation. Endogenous LPA lacks these chemical features, which thus represent the crucial elements of nonlipid agonists that potently activate LPA. This study provides detailed mechanistic insights into the ligand recognition and activation of LPA by nonlipid agonists, expanding the scope for drug development targeting the LPA receptors. PubMed: 39506093DOI: 10.1038/s42003-024-07152-y PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.86 Å) |
Structure validation
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