8TB0
Cryo-EM Structure of GPR61-G protein complex stabilized by scFv16
Summary for 8TB0
| Entry DOI | 10.2210/pdb8tb0/pdb |
| EMDB information | 41144 |
| Descriptor | Single-chain Fv16, GPR61 fused to dominant negative G alpha S/I N18 chimera, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (4 entities in total) |
| Functional Keywords | gpr61, gpcr, signaling complex, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 185266.89 |
| Authors | |
| Primary citation | Lees, J.A.,Dias, J.M.,Rajamohan, F.,Fortin, J.P.,O'Connor, R.,Kong, J.X.,Hughes, E.A.G.,Fisher, E.L.,Tuttle, J.B.,Lovett, G.,Kormos, B.L.,Unwalla, R.J.,Zhang, L.,Dechert Schmitt, A.M.,Zhou, D.,Moran, M.,Stevens, K.A.,Fennell, K.F.,Varghese, A.E.,Maxwell, A.,Cote, E.E.,Zhang, Y.,Han, S. An inverse agonist of orphan receptor GPR61 acts by a G protein-competitive allosteric mechanism. Nat Commun, 14:5938-5938, 2023 Cited by PubMed Abstract: GPR61 is an orphan GPCR related to biogenic amine receptors. Its association with phenotypes relating to appetite makes it of interest as a druggable target to treat disorders of metabolism and body weight, such as obesity and cachexia. To date, the lack of structural information or a known biological ligand or tool compound has hindered comprehensive efforts to study GPR61 structure and function. Here, we report a structural characterization of GPR61, in both its active-like complex with heterotrimeric G protein and in its inactive state. Moreover, we report the discovery of a potent and selective small-molecule inverse agonist against GPR61 and structural elucidation of its allosteric binding site and mode of action. These findings offer mechanistic insights into an orphan GPCR while providing both a structural framework and tool compound to support further studies of GPR61 function and modulation. PubMed: 37741852DOI: 10.1038/s41467-023-41646-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.47 Å) |
Structure validation
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