Critical role of the finger loop in arrestin binding to the receptors.

Zheng C, Tholen J, Gurevich VV
PLoS One. 2019 14 (3): e0213792

PMID: 30875392 · PMCID: PMC6420155 · DOI:10.1371/journal.pone.0213792

We tested the interactions with four different G protein-coupled receptors (GPCRs) of arrestin-3 mutants with substitutions in the four loops, three of which contact the receptor in the structure of the arrestin-1-rhodopsin complex. Point mutations in the loop at the distal tip of the N-domain (Glu157Ala), in the C-loop (Phe255Ala), back loop (Lys313Ala), and one of the mutations in the finger loop (Gly65Pro) had mild variable effects on receptor binding. In contrast, the deletion of Gly65 at the beginning of the finger loop reduced the binding to all GPCRs tested, with the binding to dopamine D2 receptor being affected most dramatically. Thus, the presence of a glycine at the beginning of the finger loop appears to be critical for the arrestin-receptor interaction.

MeSH Terms (11)

Amino Acid Sequence Arrestins HEK293 Cells Humans Point Mutation Protein Conformation Receptor, Muscarinic M2 Receptors, Adrenergic, beta-2 Receptors, Dopamine D1 Receptors, Dopamine D2 Sequence Homology

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