| Autor: |
Joshua A. Lees, João M. Dias, Francis Rajamohan, Jean-Philippe Fortin, Rebecca O’Connor, Jimmy X. Kong, Emily A. G. Hughes, Ethan L. Fisher, Jamison B. Tuttle, Gabrielle Lovett, Bethany L. Kormos, Rayomand J. Unwalla, Lei Zhang, Anne-Marie Dechert Schmitt, Dahui Zhou, Michael Moran, Kimberly A. Stevens, Kimberly F. Fennell, Alison E. Varghese, Andrew Maxwell, Emmaline E. Cote, Yuan Zhang, Seungil Han |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-12 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-41646-3 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full text from SpringerLink