Arrestin binding to calmodulin: a direct interaction between two ubiquitous signaling proteins. J Mol Biol 2006 Dec 15;364(5):955-63
Date
10/24/2006Pubmed ID
17054984Pubmed Central ID
PMC1783800DOI
10.1016/j.jmb.2006.09.075Scopus ID
2-s2.0-33751079911 (requires institutional sign-in at Scopus site) 72 CitationsAbstract
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 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
ArrestinsBinding Sites
Calcium
Calmodulin
Electron Spin Resonance Spectroscopy
Humans
Immunoprecipitation
Mutagenesis, Site-Directed
Mutation
Protein Binding
Protein Conformation