Benjamin Spiller
Last active: 4/10/2019

Crystal structure of arrestin-3 reveals the basis of the difference in receptor binding between two non-visual subtypes.

Zhan X, Gimenez LE, Gurevich VV, Spiller BW
J Mol Biol. 2011 406 (3): 467-78

PMID: 21215759 · PMCID: PMC3034793 · DOI:10.1016/j.jmb.2010.12.034

Arrestins are multi-functional proteins that regulate signaling and trafficking of the majority of G protein-coupled receptors (GPCRs), as well as sub-cellular localization and activity of many other signaling proteins. We report the first crystal structure of arrestin-3, solved at 3.0 Å resolution. Arrestin-3 is an elongated two-domain molecule with overall fold and key inter-domain interactions that hold the free protein in the basal conformation similar to the other subtypes. Arrestin-3 is the least selective member of the family, binding a wide variety of GPCRs with high affinity and demonstrating lower preference for active phosphorylated forms of the receptors. In contrast to the other three arrestins, part of the receptor-binding surface in the arrestin-3 C-domain does not form a contiguous β-sheet, which is consistent with increased flexibility. By swapping the corresponding elements between arrestin-2 and arrestin-3 we show that the presence of this loose structure is correlated with reduced arrestin selectivity for activated receptors, consistent with a conformational change in this β-sheet upon receptor binding.

Copyright © 2011 Elsevier Ltd. All rights reserved.

MeSH Terms (10)

Animals Arrestins Binding Sites Cattle Crystallization Protein Binding Protein Conformation Protein Structure, Tertiary Receptors, G-Protein-Coupled Structure-Activity Relationship

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