Arrestins: A Small Family of Multi-Functional Proteins

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jun 19

PMID 38892473

Authors

Vsevolod V Gurevich

Affiliations

Soon will be listed here.

Abstract

The first member of the arrestin family, visual arrestin-1, was discovered in the late 1970s. Later, the other three mammalian subtypes were identified and cloned. The first described function was regulation of G protein-coupled receptor (GPCR) signaling: arrestins bind active phosphorylated GPCRs, blocking their coupling to G proteins. It was later discovered that receptor-bound and free arrestins interact with numerous proteins, regulating GPCR trafficking and various signaling pathways, including those that determine cell fate. Arrestins have no enzymatic activity; they function by organizing multi-protein complexes and localizing their interaction partners to particular cellular compartments. Today we understand the molecular mechanism of arrestin interactions with GPCRs better than the mechanisms underlying other functions. However, even limited knowledge enabled the construction of signaling-biased arrestin mutants and extraction of biologically active monofunctional peptides from these multifunctional proteins. Manipulation of cellular signaling with arrestin-based tools has research and likely therapeutic potential: re-engineered proteins and their parts can produce effects that conventional small-molecule drugs cannot.

Citing Articles

The Role of Individual Residues in the N-Terminus of Arrestin-1 in Rhodopsin Binding.

Vishnivetskiy S, Paul T, Gurevich E, Gurevich V Int J Mol Sci. 2025; 26(2).

PMID: 39859432 PMC: 11765510. DOI: 10.3390/ijms26020715.

A small molecule enhances arrestin-3 binding to the β-adrenergic receptor.

Kurt H, Akyol A, Son C, Zheng C, Gado I, Meli M bioRxiv. 2024; .

PMID: 39713392 PMC: 11661165. DOI: 10.1101/2024.12.12.628161.

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