Solo vs. Chorus: Monomers and Oligomers of Arrestin Proteins

Abstract

Three out of four subtypes of arrestin proteins expressed in mammals self-associate, each forming oligomers of a distinct kind. Monomers and oligomers have different subcellular localization and distinct biological functions. Here we summarize existing evidence regarding arrestin oligomerization and discuss specific functions of monomeric and oligomeric forms, although too few of the latter are known. The data on arrestins highlight biological importance of oligomerization of signaling proteins. Distinct modes of oligomerization might be an important contributing factor to the functional differences among highly homologous members of the arrestin protein family.

Structural snapshots uncover a lock-and-key type conserved activation mechanism of β-arrestins by GPCRs

“…An intriguing observation in these structural snapshots is novel dimer and trimer assemblies of βarrs. Although βarrs have strong propensity to adopt different oligomeric states (Chen et al, 2014;Chen et al, 2021;Gurevich and Gurevich, 2022), the dimer and trimer interfaces observed here differ significantly from previously reported interfaces (Chen et al, 2017;Chen et al, 2014;Chen et al, 2021) (Figure S7). The overall buried surface area in dimer and trimer assemblies are approximately 1500 Å 2 and 4500 Å 2 , respectively, suggesting a robust and stable oligomeric arrangement.…”

Structural snapshots uncover a key phosphorylation motif in GPCRs driving β-arrestin activation

“…An intriguing observation in these structural snapshots is novel dimer and trimer assemblies of βarrs. Although βarrs have a strong propensity to adopt different oligomeric states, 55 – 57 the dimer and trimer interfaces observed here differ significantly from previously reported interfaces 34 , 56 , 57 (Figure S7). The overall buried surface area in dimer and trimer assemblies are approximately 1,500 and 4,500 Å 2 , respectively, suggesting a robust and stable oligomeric arrangement.…”

Molecular insights into atypical modes of β-arrestin interaction with seven transmembrane receptors

“…Stabilizing chaperones such as Fab30 may preferentially recognize some of these conformations better than the others. βarrs have a strong tendency to form various oligomeric states including dimers, trimers, tetramers, and even higher-order oligomers ( 54 , 55 ), although previous structures of βarr2 either bound to IP6 ( 56 ) or GPCR phosphopeptides have revealed trimers ( 17 ). Future work should explore whether the dimeric arrangement observed here is specific to D6R.…”