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Identification of receptor binding-induced conformational changes in non-visual arrestins. J Biol Chem 2014 Jul 25;289(30):20991-1002

Date

05/29/2014

Pubmed ID

24867953

Pubmed Central ID

PMC4110305

DOI

10.1074/jbc.M114.560680

Scopus ID

2-s2.0-84905370362   31 Citations

Abstract

The non-visual arrestins, arrestin-2 and arrestin-3, belong to a small family of multifunctional cytosolic proteins. Non-visual arrestins interact with hundreds of G protein-coupled receptors (GPCRs) and regulate GPCR desensitization by binding active phosphorylated GPCRs and uncoupling them from heterotrimeric G proteins. Recently, non-visual arrestins have been shown to mediate G protein-independent signaling by serving as adaptors and scaffolds that assemble multiprotein complexes. By recruiting various partners, including trafficking and signaling proteins, directly to GPCRs, non-visual arrestins connect activated receptors to diverse signaling pathways. To investigate arrestin-mediated signaling, a structural understanding of arrestin activation and interaction with GPCRs is essential. Here we identified global and local conformational changes in the non-visual arrestins upon binding to the model GPCR rhodopsin. To detect conformational changes, pairs of spin labels were introduced into arrestin-2 and arrestin-3, and the interspin distances in the absence and presence of the receptor were measured by double electron electron resonance spectroscopy. Our data indicate that both non-visual arrestins undergo several conformational changes similar to arrestin-1, including the finger loop moving toward the predicted location of the receptor in the complex as well as the C-tail release upon receptor binding. The arrestin-2 results also suggest that there is no clam shell-like closure of the N- and C-domains and that the loop containing residue 136 (homolog of 139 in arrestin-1) has high flexibility in both free and receptor-bound states.

Author List

Zhuo Y, Vishnivetskiy SA, Zhan X, Gurevich VV, Klug CS

Author

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

Arrestins
Humans
Protein Structure, Secondary
Protein Structure, Tertiary
Rhodopsin
Signal Transduction
Spin Labels
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75