The Role of Arrestin-1 Middle Loop in Rhodopsin Binding

Date

2022-11-11

Authors

Vishnivetskiy, Sergey A.
Huh, Elizabeth K.
Karnam, Preethi C.
Oviedo, Samantha
Gurevich, Eugenia V.
Gurevich, Vsevolod V.

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Abstract

Arrestins preferentially bind active phosphorylated G protein-coupled receptors (GPCRs). The middle loop, highly conserved in all arrestin subtypes, is localized in the central crest on the GPCR-binding side. Upon receptor binding, it directly interacts with bound GPCR and demonstrates the largest movement of any arrestin element in the structures of the complexes. Comprehensive mutagenesis of the middle loop of rhodopsin-specific arrestin-1 suggests that it primarily serves as a suppressor of binding to non-preferred forms of the receptor. Several mutations in the middle loop increase the binding to unphosphorylated light-activated rhodopsin severalfold, which makes them candidates for improving enhanced phosphorylation-independent arrestins. The data also suggest that enhanced forms of arrestin do not bind GPCRs exactly like the wild-type protein. Thus, the structures of the arrestin-receptor complexes, in all of which different enhanced arrestin mutants and reengineered receptors were used, must be interpreted with caution.

Description

Keywords

arrestin, GPCR, mutagenesis, protein-protein interactions, receptor binding, selectivity

Citation

International Journal of Molecular Sciences 23 (22): 13887 (2022)

Department

Chemistry