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Arrestin binding to calmodulin: a direct interaction between two ubiquitous signaling proteins. J Mol Biol 2006 Dec 15;364(5):955-63

Date

10/24/2006

Pubmed ID

17054984

Pubmed Central ID

PMC1783800

DOI

10.1016/j.jmb.2006.09.075

Scopus ID

2-s2.0-33751079911 (requires institutional sign-in at Scopus site)   72 Citations

Abstract

Arrestins serve as multi-functional regulators of G-protein coupled receptors, interacting with hundreds of different receptor subtypes and a variety of other signaling proteins. Here we identify calmodulin as a novel arrestin interaction partner using three independent methods in vitro and in cells. Arrestin preferentially binds calcium-loaded calmodulin with a Kd value of approximately 7 microM, which is within range of endogenous calmodulin concentrations. The calmodulin binding site is localized on the concave side of the C-domain and a loop in the center of the arrestin molecule, significantly overlapping with receptor and microtubule-binding sites. Using purified proteins, we found that arrestins sequester calmodulin, preventing its binding to microtubules. Nanomolar affinity of arrestins for their cognate receptors makes calmodulin an ineffective competitor for arrestin binding at relatively high receptor concentrations. The arrestin-calmodulin interaction likely regulates the localization of both proteins and their availability for other interaction partners.

Author List

Wu N, Hanson SM, Francis DJ, Vishnivetskiy SA, Thibonnier M, Klug CS, Shoham M, Gurevich VV

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
Binding Sites
Calcium
Calmodulin
Electron Spin Resonance Spectroscopy
Humans
Immunoprecipitation
Mutagenesis, Site-Directed
Mutation
Protein Binding
Protein Conformation