Mutational analysis of G-protein coupled receptor – FFA2 |
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Authors: | Gayathri Swaminath Peter Jaeckel Qi Guo Mario Cardozo Jennifer Weiszmann Richard Lindberg Yingcai Wang Ralf Schwandner Yang Li |
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Institution: | aAmgen Inc., 1120 Veterans Blvd., South San Francisco, CA 94080, USA;bAmgen Research-GMBH, Regensburg, Germany |
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Abstract: | FFA2 (GPR43) is a receptor for short-chain fatty acids (SCFAs), acetate, and propionate. FFA2 is predominantly expressed in islets, a subset of immune cells, adipocytes, and the gastrointestinal tract which suggest a possible role in inflammatory and metabolic conditions. We have previously described the identification and characterization of novel phenylacetamides as allosteric agonists of FFA2. In the current study, we have investigated the molecular determinants contributing to receptor activation with the endogenous and synthetic ligands as well as allosteric interactions between these two sites. The mutational analysis revealed previously unidentified sites that may allosterically regulate orthosteric ligand’s function as well as residues potentially important for the interactions between orthosteric and allosteric binding sites. |
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Keywords: | FFAR2 FFA2 GPR43 Allosteric agonist Short-chain fatty acids AMG7703 |
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