7TD1
Lysophosphatidic acid receptor 1-Gi complex bound to LPA, state a
Summary for 7TD1
| Entry DOI | 10.2210/pdb7td1/pdb |
| EMDB information | 25820 |
| Descriptor | Lysophosphatidic acid receptor 1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(i) subunit alpha-1, ... (5 entities in total) |
| Functional Keywords | gpcr, complex, lipid, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 128596.20 |
| Authors | Liu, S.,Paknejad, N.,Zhu, L.,Kihara, Y.,Ray, D.,Chun, J.,Liu, W.,Hite, R.K.,Huang, X.Y. (deposition date: 2021-12-30, release date: 2022-02-09, Last modification date: 2024-10-23) |
| Primary citation | Liu, S.,Paknejad, N.,Zhu, L.,Kihara, Y.,Ray, M.,Chun, J.,Liu, W.,Hite, R.K.,Huang, X.Y. Differential activation mechanisms of lipid GPCRs by lysophosphatidic acid and sphingosine 1-phosphate. Nat Commun, 13:731-731, 2022 Cited by PubMed Abstract: Lysophospholipids are bioactive lipids and can signal through G-protein-coupled receptors (GPCRs). The best studied lysophospholipids are lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). The mechanisms of lysophospholipid recognition by an active GPCR, and the activations of lysophospholipid GPCR-G-protein complexes remain unclear. Here we report single-particle cryo-EM structures of human S1P receptor 1 (S1P) and heterotrimeric G complexes formed with bound S1P or the multiple sclerosis (MS) treatment drug Siponimod, as well as human LPA receptor 1 (LPA) and G complexes in the presence of LPA. Our structural and functional data provide insights into how LPA and S1P adopt different conformations to interact with their cognate GPCRs, the selectivity of the homologous lipid GPCRs for S1P versus LPA, and the different activation mechanisms of these GPCRs by LPA and S1P. Our studies also reveal specific optimization strategies to improve the MS-treating S1P-targeting drugs. PubMed: 35136060DOI: 10.1038/s41467-022-28417-2 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.08 Å) |
Structure validation
Download full validation report
