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- W4281488327 endingPage "e202201439" @default.
- W4281488327 startingPage "e202201439" @default.
- W4281488327 abstract "G protein-coupled receptors (GPCRs) induce signal transduction pathways through coupling to four main subtypes of G proteins (Gs, Gi, Gq, and G12/13), selectively. However, G protein selective activation mechanisms and residual determinants in GPCRs have remained obscure. Herein, we performed extensive phylogenetic analysis and identified specifically conserved residues for the aminergic receptors having similar coupling profiles. By integrating our methodology of differential evolutionary conservation of G protein-specific amino acids with structural analyses, we identified specific activation networks for Gs, Gi1, Go, and Gq To validate that these networks could determine coupling selectivity we further analyzed Gs-specific activation network and its association with Gs selectivity. Through molecular dynamics simulations, we showed that previously uncharacterized Glycine at position 7x41 plays an important role in receptor activation and it may determine Gs coupling selectivity by facilitating a larger TM6 movement. Finally, we gathered our results into a comprehensive model of G protein selectivity called sequential switches of activation describing three main molecular switches controlling GPCR activation: ligand binding, G protein selective activation mechanisms, and G protein contact." @default.
- W4281488327 created "2022-05-26" @default.
- W4281488327 creator A5036514234 @default.
- W4281488327 creator A5046768485 @default.
- W4281488327 creator A5069814829 @default.
- W4281488327 creator A5080235407 @default.
- W4281488327 date "2022-05-25" @default.
- W4281488327 modified "2023-09-26" @default.
- W4281488327 title "Evolutionary association of receptor-wide amino acids with G protein–coupling selectivity in aminergic GPCRs" @default.
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- W4281488327 doi "https://doi.org/10.26508/lsa.202201439" @default.
- W4281488327 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35613896" @default.
- W4281488327 hasPublicationYear "2022" @default.
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