Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Few residues within an extensive binding interface drive receptor interaction and determine the specificity of arrestin proteins. J Biol Chem 2011 Jul 08;286(27):24288-99



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-79959862379   79 Citations


Arrestins bind active phosphorylated forms of G protein-coupled receptors, terminating G protein activation, orchestrating receptor trafficking, and redirecting signaling to alternative pathways. Visual arrestin-1 preferentially binds rhodopsin, whereas the two non-visual arrestins interact with hundreds of G protein-coupled receptor subtypes. Here we show that an extensive surface on the concave side of both arrestin-2 domains is involved in receptor binding. We also identified a small number of residues on the receptor binding surface of the N- and C-domains that largely determine the receptor specificity of arrestins. We show that alanine substitution of these residues blocks the binding of arrestin-1 to rhodopsin in vitro and of arrestin-2 and -3 to β2-adrenergic, M2 muscarinic cholinergic, and D2 dopamine receptors in intact cells, suggesting that these elements critically contribute to the energy of the interaction. Thus, in contrast to arrestin-1, where direct phosphate binding is crucial, the interaction of non-visual arrestins with their cognate receptors depends to a lesser extent on phosphate binding and more on the binding to non-phosphorylated receptor elements.

Author List

Vishnivetskiy SA, Gimenez LE, Francis DJ, Hanson SM, Hubbell WL, Klug CS, Gurevich VV


Candice S. Klug PhD Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Substitution
Binding Sites
Mutation, Missense
Peptide Mapping
Protein Structure, Tertiary
Receptors, G-Protein-Coupled
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc