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- W4285807787 endingPage "102279" @default.
- W4285807787 startingPage "102279" @default.
- W4285807787 abstract "G protein-coupled receptor (GPCR) kinases (GRKs) and arrestins interact with agonist-bound GPCRs to promote receptor desensitization and downregulation. They also trigger signaling cascades distinct from those of heterotrimeric G proteins. Biased agonists for GPCRs that favor either heterotrimeric G protein or GRK/arrestin signaling are of profound pharmacological interest because they could usher in a new generation of drugs with greatly reduced side effects. One mechanism by which biased agonism might occur is by stabilizing receptor conformations that preferentially bind to GRKs and/or arrestins. In this review, we explore this idea by comparing structures of GPCRs bound to heterotrimeric G proteins with those of the same GPCRs in complex with arrestins and GRKs. The arrestin and GRK complexes all exhibit high conformational heterogeneity, which is likely a consequence of their unusual ability to adapt and bind to hundreds of different GPCRs. This dynamic behavior, along with the experimental tactics required to stabilize GPCR complexes for biophysical analysis, confounds these comparisons, but some possible molecular mechanisms of bias are beginning to emerge. We also examine if and how the recent structures advance our understanding of how arrestins parse the phosphorylation barcodes installed in the intracellular loops and tails of GPCRs by GRKs. In the future, structural analyses of arrestins in complex with intact receptors that have well-defined native phosphorylation barcodes, such as those installed by the two nonvisual subfamilies of GRKs, will be particularly illuminating." @default.
- W4285807787 created "2022-07-19" @default.
- W4285807787 creator A5037144273 @default.
- W4285807787 creator A5043435719 @default.
- W4285807787 date "2022-09-01" @default.
- W4285807787 modified "2023-10-14" @default.
- W4285807787 title "G protein–coupled receptor interactions with arrestins and GPCR kinases: The unresolved issue of signal bias" @default.
- W4285807787 cites W1599069035 @default.
- W4285807787 cites W1955508706 @default.
- W4285807787 cites W1967352670 @default.
- W4285807787 cites W1971929424 @default.
- W4285807787 cites W1989707466 @default.
- W4285807787 cites W1991459803 @default.
- W4285807787 cites W1994539207 @default.
- W4285807787 cites W2017875329 @default.
- W4285807787 cites W2018506708 @default.
- W4285807787 cites W2018981978 @default.
- W4285807787 cites W2026493203 @default.
- W4285807787 cites W2038368021 @default.
- W4285807787 cites W2040130844 @default.
- W4285807787 cites W2049834824 @default.
- W4285807787 cites W2052288973 @default.
- W4285807787 cites W2053320675 @default.
- W4285807787 cites W2060514775 @default.
- W4285807787 cites W2069547389 @default.
- W4285807787 cites W2077936290 @default.
- W4285807787 cites W2080192851 @default.
- W4285807787 cites W2082039166 @default.
- W4285807787 cites W2085022379 @default.
- W4285807787 cites W2087663632 @default.
- W4285807787 cites W2089291239 @default.
- W4285807787 cites W2092074623 @default.
- W4285807787 cites W2121473111 @default.
- W4285807787 cites W2123381928 @default.
- W4285807787 cites W2149464986 @default.
- W4285807787 cites W2165775221 @default.
- W4285807787 cites W2169279934 @default.
- W4285807787 cites W2505532605 @default.
- W4285807787 cites W2589588042 @default.
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- W4285807787 cites W2626714978 @default.
- W4285807787 cites W2734817732 @default.
- W4285807787 cites W2739933313 @default.
- W4285807787 cites W2747027054 @default.
- W4285807787 cites W2767610564 @default.
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- W4285807787 cites W2795707628 @default.
- W4285807787 cites W2800175679 @default.
- W4285807787 cites W2801711247 @default.
- W4285807787 cites W2917973990 @default.
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- W4285807787 cites W2988065622 @default.
- W4285807787 cites W2989686935 @default.
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- W4285807787 cites W3035794825 @default.
- W4285807787 cites W3037696572 @default.
- W4285807787 cites W3037726610 @default.
- W4285807787 cites W3077605905 @default.
- W4285807787 cites W3085020181 @default.
- W4285807787 cites W3085560188 @default.
- W4285807787 cites W3110608978 @default.
- W4285807787 cites W3111806298 @default.
- W4285807787 cites W3111854290 @default.
- W4285807787 cites W3129083073 @default.
- W4285807787 cites W3138819644 @default.
- W4285807787 cites W3156609721 @default.
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- W4285807787 cites W3180740192 @default.
- W4285807787 cites W3181632501 @default.
- W4285807787 cites W4212914636 @default.
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- W4285807787 cites W4253117833 @default.
- W4285807787 cites W4285083066 @default.
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- W4285807787 doi "https://doi.org/10.1016/j.jbc.2022.102279" @default.
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