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
Date
04/08/2011Pubmed ID
21471193Pubmed Central ID
PMC3129209DOI
10.1074/jbc.M110.213835Scopus ID
2-s2.0-79959862379 (requires institutional sign-in at Scopus site) 104 CitationsAbstract
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 VVAuthor
Candice S. Klug PhD Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SubstitutionAnimals
Arrestin
Binding Sites
Cattle
Humans
Mutation, Missense
Peptide Mapping
Protein Structure, Tertiary
Receptors, G-Protein-Coupled
