ArticleThe Journal of biological chemistry2012
Manipulation of very few receptor discriminator residues greatly enhances receptor specificity of non-visual arrestins.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 62 citations in OpenAlex.
- Arrestins: A Small Family of Multi-Functional Proteins.International journal of molecular sciences · 2024Review
- Review
- The finger loop as an activation sensor in arrestin.Journal of neurochemistry · 2021Article
- Receptor-Arrestin Interactions: The GPCR Perspective.Biomolecules · 2021Review
- Lysine in the lariat loop of arrestins does not serve as phosphate sensor.Journal of neurochemistry · 2021Article
- Review
- Article
- Targeting arrestin interactions with its partners for therapeutic purposes.Advances in protein chemistry and structural biology · 2020Review
- Plethora of functions packed into 45 kDa arrestins: biological implications and possible therapeutic strategies.Cellular and molecular life sciences : CMLS · 2019Review
- The structural basis of the arrestin binding to GPCRs.Molecular and cellular endocrinology · 2019Review
- Using In Vitro Pull-Down and In-Cell Overexpression Assays to Study Protein Interactions with Arrestin.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Article
- GPCR Signaling Regulation: The Role of GRKs and Arrestins.Frontiers in pharmacology · 2019Review
- Arrestin mutations: Some cause diseases, others promise cure.Progress in molecular biology and translational science · 2019Review
- Structure and dynamics of GPCR signaling complexes.Nature structural & molecular biology · 2018Review
- Arrestins: Introducing Signaling Bias Into Multifunctional Proteins.Progress in molecular biology and translational science · 2018Review
- Molecular Mechanisms of GPCR Signaling: A Structural Perspective.International journal of molecular sciences · 2017Review
- Differential manipulation of arrestin-3 binding to basal and agonist-activated G protein-coupled receptors.Cellular signalling · 2017Article
- Uncovering missing pieces: duplication and deletion history of arrestins in deuterostomes.BMC evolutionary biology · 2017Article
- The Diverse Roles of Arrestin Scaffolds in G Protein-Coupled Receptor Signaling.Pharmacological reviews · 2017Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Based on the identification of residues that determine receptor selectivity of arrestins and the analysis of the evolution in the arrestin family, we introduced 10 mutations of "receptor discriminator" residues in arrestin-3. The recruitment of these mutants to M2 muscarinic (M2R), D1 (D1R) and D2 (D2R) dopamine, and β(2)-adrenergic receptors (β(2)AR) was assessed using bioluminescence resonance energy transfer-based assays in cells. Seven of 10 mutations differentially affected arrestin-3 binding to individual receptors. D260K and Q262P reduced the binding to β(2)AR, much more than to other receptors. The combination D260K/Q262P virtually eliminated β(2)AR binding while preserving the interactions with M2R, D1R, and D2R. Conversely, Y239T enhanced arrestin-3 binding to β(2)AR and reduced the binding to M2R, D1R, and D2R, whereas Q256Y selectively reduced recruitment to D2R. The Y239T/Q256Y combination virtually eliminated the binding to D2R and reduced the binding to β(2)AR and M2R, yielding a mutant with high selectivity for D1R. Eleven of 12 mutations significantly changed the binding to light-activated phosphorhodopsin. Thus, manipulation of key residues on the receptor-binding surface modifies receptor preference, enabling the construction of non-visual arrestins specific for particular receptor subtypes. These findings pave the way to the construction of signaling-biased arrestins targeting the receptor of choice for research or therapeutic purposes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.