7SUS
Crystal structure of Apelin receptor in complex with small molecule
Summary for 7SUS
| Entry DOI | 10.2210/pdb7sus/pdb |
| Descriptor | Apelin receptor, with Rubredoxin insertion, ZINC ION, (1R,2S)-N-[4-(2,6-dimethoxyphenyl)-5-(6-methylpyridin-2-yl)-1,2,4-triazol-3-yl]-1-(5-methylpyrimidin-2-yl)-1-oxidanyl-propane-2-sulfonamide, ... (5 entities in total) |
| Functional Keywords | gpcr, class a gpcr, small molecule, membrane protein, apelin receptor |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 47384.14 |
| Authors | Xu, F.,Yue, Y.,Liu, L.E.,Han, G.W.,Hanson, M. (deposition date: 2021-11-18, release date: 2022-07-27, Last modification date: 2024-10-09) |
| Primary citation | Yue, Y.,Liu, L.,Wu, L.J.,Wu, Y.,Wang, L.,Li, F.,Liu, J.,Han, G.W.,Chen, B.,Lin, X.,Brouillette, R.L.,Breault, E.,Longpre, J.M.,Shi, S.,Lei, H.,Sarret, P.,Stevens, R.C.,Hanson, M.A.,Xu, F. Structural insight into apelin receptor-G protein stoichiometry. Nat.Struct.Mol.Biol., 29:688-697, 2022 Cited by PubMed Abstract: The technique of cryogenic-electron microscopy (cryo-EM) has revolutionized the field of membrane protein structure and function with a focus on the dominantly observed molecular species. This report describes the structural characterization of a fully active human apelin receptor (APJR) complexed with heterotrimeric G protein observed in both 2:1 and 1:1 stoichiometric ratios. We use cryo-EM single-particle analysis to determine the structural details of both species from the same sample preparation. Protein preparations, in the presence of the endogenous peptide ligand ELA or a synthetic small molecule, both demonstrate these mixed stoichiometric states. Structural differences in G protein engagement between dimeric and monomeric APJR suggest a role for the stoichiometry of G protein-coupled receptor- (GPCR-)G protein coupling on downstream signaling and receptor pharmacology. Furthermore, a small, hydrophobic dimer interface provides a starting framework for additional class A GPCR dimerization studies. Together, these findings uncover a mechanism of versatile regulation through oligomerization by which GPCRs can modulate their signaling. PubMed: 35817871DOI: 10.1038/s41594-022-00797-5 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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