Crystal Structure of Arrestin-3 Reveals the Basis of the Difference in Receptor Binding Between Two Non-visual Subtypes

JOURNAL OF MOLECULAR BIOLOGY

卷:406

Article

Zhan, Xuanzhi¹  Gimenez, Luis E.¹  Gurevich, Vsevolod V.¹  Spiller, Benjamin W.^1,2 

[1] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Dept Microbiol & Immunol, Nashville, TN 37232 USA

关键词: arrestin;    stability;    BRET;    self-association;    GPCR;   

DOI  :  10.1016/j.jmb.2010.12.034

来源: Elsevier

【 摘 要 】

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 angstrom 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 beta-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 beta-sheet upon receptor binding. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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