GPCRs arrestin binding

The primary function of GRK-mediated receptor phosphorylation is to promote the recruitment of another crucial protein, named P-arrestin,to the activated receptor. Arrestin binds to GPCRs and inhibits further coupling to G proteins hence desensitizing the response (Ferguson 2001 Penn et al. 2001 Pierce et al. 2002 Maudsley et al. 2005). P-arrestin belongs to the arrestin family of which four members have been identified (Gurevich et al. 2008). 

Fig. 5.5 Desensitization of the activated (Tadrenergic receptor, PAR. PARK is the p-adrenergic receptor kinase, as and py are the activated a-subunit and the Py-subunits of the heterotrimeric G protein, Gg. AC is the activated effector, the enzyme adenylyl cyclase. Phosphorylation of activated GPCRs enhances binding of a family of proteins, the arrestins, which prevent access of G proteins and uncouple the receptor from G proteins. The arrestin involved in the desensitization of the P-adrenergic receptor is p-arrestin. (Reproduction of this scheme has been made possible through the generosity of Professor Martin Lohse, Department of Pharmacology, University of Wurzburg, Medical School.)...

Arrestins act as adaptor proteins that bind to phos-phorylated G protein-coupled receptors (GPCR) and link the receptors to clathrin-coated pits. (3-Arrestins are essential in the internalization of many GPCRs. 

Despite the broad range of possible actions of GPCRs, they all share a common seven a-helical transmembrane motif of the structure. The ligand binding site is located either at the extracellular region or within the transmembrane a-helical bundle, and the cytoplasmic loops are responsible for coupling to G proteins and activate them (GPCRs act in an enzymatic way) whereas other proteins like arrestins stop enzymatic action of these receptors. 

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