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Regulation of G Protein-Coupled Receptor Kinases by Phospholipids

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Abstract:

G protein coupled-receptor (GPCR) kinases (GRKs) initiate the deactivation of GPCRs by phosphorylating their cytoplasmic loops and C-terminal tails. They are regulated not only by allosteric interactions with activated GPCRs, but also by the membrane environment itself. Herein we describe how the various GRKs are recruited to lipid bilayers and, where evident, how specific anionic phospholipids help regulate their activity. Using crystal structures representing each of the three vertebrate GRK subfamilies, we map the lipid binding sites in order to better understand how these enzymes are oriented at the cell surface. This analysis suggests that GRKs bind lipid and active GPCRs in a coordinated manner.
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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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