Allosteric rescuing of loss-of-function FFAR2 mutations.
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Swaminath G, Jaeckel P, Guo Q, Cardozo M, Weiszmann J, Lindberg R, Wang Y, Schwandner R, Li Y
Allosteric rescuing of loss-of-function FFAR2 mutations.
FEBS Lett. 2010 Oct 8;584(19):4208-14. doi: 10.1016/j.febslet.2010.09.007. Epub 2010 Sep 17.
- PubMed ID
- 20837008 [ View in PubMed]
- Abstract
FFAR2 (GPR43) is a receptor for short-chain fatty acids (SCFAs), acetate and propionate. In the current study, we investigate the molecular determinants contributing to receptor activation by endogenous ligands. Mutational analysis revealed several important residues located in transmembrane domains (TM) 3, 4, 5, 6, and 7 for acetate binding. Interestingly, mutations that abolished acetate activity, including the mutation in the well-conserved D(E)RY motif, could be rescued by a recently identified synthetic allosteric agonist. These findings provide additional insight into agonist binding and activation which may aid in designing allosteric ligands for targeting receptor function in various diseases.