7C4S
Sphingosine-1-phosphate receptor 3 with a natural ligand.
Summary for 7C4S
| Entry DOI | 10.2210/pdb7c4s/pdb |
| Descriptor | Antibody Fab fragment light chain, Antibody Fab fragment heavy chain, Sphingosine 1-phosphate receptor 3, ... (4 entities in total) |
| Functional Keywords | g protein-coupled receptor, signaling protein, agonist, natural ligand, lysophospholipid, regulator of immune system and vascular integrity., membrane protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 179359.97 |
| Authors | |
| Primary citation | Maeda, S.,Shiimura, Y.,Asada, H.,Hirata, K.,Luo, F.,Nango, E.,Tanaka, N.,Toyomoto, M.,Inoue, A.,Aoki, J.,Iwata, S.,Hagiwara, M. Endogenous agonist-bound S1PR3 structure reveals determinants of G protein-subtype bias. Sci Adv, 7:-, 2021 Cited by PubMed Abstract: Sphingosine-1-phosphate (S1P) regulates numerous important physiological functions, including immune response and vascular integrity, via its cognate receptors (S1PR1 to S1PR5); however, it remains unclear how S1P activates S1PRs upon binding. Here, we determined the crystal structure of the active human S1PR3 in complex with its natural agonist S1P at 3.2-Å resolution. S1P exhibits an unbent conformation in the long tunnel, which penetrates through the receptor obliquely. Compared with the inactive S1PR1 structure, four residues surrounding the alkyl tail of S1P (the "quartet core") exhibit orchestrating rotamer changes that accommodate the moiety, thereby inducing an active conformation. In addition, we reveal that the quartet core determines G protein selectivity of S1PR3. These results offer insight into the structural basis of activation and biased signaling in G protein-coupled receptors and will help the design of biased ligands for optimized therapeutics. PubMed: 34108205DOI: 10.1126/sciadv.abf5325 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.2 Å) |
Structure validation
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