Summary for 9IPV
| Entry DOI | 10.2210/pdb9ipv/pdb |
| EMDB information | 60782 60783 60784 |
| Descriptor | Guanine nucleotide-binding protein G(i) subunit alpha-1, 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, ... (6 entities in total) |
| Functional Keywords | gpcr, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 170371.80 |
| Authors | Kim, J.,Ko, S.,Choi, H.-J. (deposition date: 2024-07-11, release date: 2025-04-23, Last modification date: 2025-05-07) |
| Primary citation | Kim, J.,Ko, S.,Choi, C.,Bae, J.,Byeon, H.,Seok, C.,Choi, H.J. Structural insights into small-molecule agonist recognition and activation of complement receptor C3aR. Embo J., 2025 Cited by PubMed Abstract: The complement system plays crucial roles in innate immunity and inflammatory responses. The anaphylatoxin C3a mediates pro-inflammatory and chemotactic functions through the G protein-coupled receptor C3aR. While the active structure of the C3a-C3aR-G complex has been determined, the inactive conformation and activation mechanism of C3aR remain elusive. Here we report the cryo-EM structure of ligand-free, G protein-free C3aR, providing insights into its inactive conformation. In addition, we determine the structures of C3aR in complex with the synthetic small-molecule agonist JR14a in two distinct conformational states: a G protein-free intermediate, and a fully active G-bound state. The structure of the active JR14a-bound C3aR reveals that JR14a engages in highly conserved interactions with C3aR, similar to the binding of the C-terminal pentapeptide of C3a, along with JR14a-specific interactions. Structural comparison of C3aR in the apo, intermediate, and fully active states provides novel insights into the conformational landscape and activation mechanism of C3aR and defines a molecular basis explaining its high basal activity. Our results may aid in the rational design of therapeutics targeting complement-related inflammatory disorders. PubMed: 40195498DOI: 10.1038/s44318-025-00429-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.53 Å) |
Structure validation
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