Structural Basis of Arrestin Selectivity for Active Phosphorylated G Protein-Coupled Receptors

Arrestins are a small family of proteins that bind G protein-coupled receptors (GPCRs). Arrestin binds to active phosphorylated GPCRs with higher affinity than to all other functional forms of the receptor, including inactive phosphorylated and active unphosphorylated. The selectivity of arrestins s...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Preethi C. Karnam, Sergey A. Vishnivetskiy, Vsevolod V. Gurevich
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	arrestin GPCR phosphorylation selectivity structure–function Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/3fcb56961cc14d2caef5ef0ab99655b7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3fcb56961cc14d2caef5ef0ab99655b7
record_format	dspace
spelling	oai:doaj.org-article:3fcb56961cc14d2caef5ef0ab99655b72021-11-25T17:57:03ZStructural Basis of Arrestin Selectivity for Active Phosphorylated G Protein-Coupled Receptors10.3390/ijms2222124811422-00671661-6596https://doaj.org/article/3fcb56961cc14d2caef5ef0ab99655b72021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12481https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Arrestins are a small family of proteins that bind G protein-coupled receptors (GPCRs). Arrestin binds to active phosphorylated GPCRs with higher affinity than to all other functional forms of the receptor, including inactive phosphorylated and active unphosphorylated. The selectivity of arrestins suggests that they must have two sensors, which detect receptor-attached phosphates and the active receptor conformation independently. Simultaneous engagement of both sensors enables arrestin transition into a high-affinity receptor-binding state. This transition involves a global conformational rearrangement that brings additional elements of the arrestin molecule, including the middle loop, in contact with a GPCR, thereby stabilizing the complex. Here, we review structural and mutagenesis data that identify these two sensors and additional receptor-binding elements within the arrestin molecule. While most data were obtained with the arrestin-1-rhodopsin pair, the evidence suggests that all arrestins use similar mechanisms to achieve preferential binding to active phosphorylated GPCRs.Preethi C. KarnamSergey A. VishnivetskiyVsevolod V. GurevichMDPI AGarticlearrestinGPCRphosphorylationselectivitystructure–functionBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12481, p 12481 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	arrestin GPCR phosphorylation selectivity structure–function Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	arrestin GPCR phosphorylation selectivity structure–function Biology (General) QH301-705.5 Chemistry QD1-999 Preethi C. Karnam Sergey A. Vishnivetskiy Vsevolod V. Gurevich Structural Basis of Arrestin Selectivity for Active Phosphorylated G Protein-Coupled Receptors
description	Arrestins are a small family of proteins that bind G protein-coupled receptors (GPCRs). Arrestin binds to active phosphorylated GPCRs with higher affinity than to all other functional forms of the receptor, including inactive phosphorylated and active unphosphorylated. The selectivity of arrestins suggests that they must have two sensors, which detect receptor-attached phosphates and the active receptor conformation independently. Simultaneous engagement of both sensors enables arrestin transition into a high-affinity receptor-binding state. This transition involves a global conformational rearrangement that brings additional elements of the arrestin molecule, including the middle loop, in contact with a GPCR, thereby stabilizing the complex. Here, we review structural and mutagenesis data that identify these two sensors and additional receptor-binding elements within the arrestin molecule. While most data were obtained with the arrestin-1-rhodopsin pair, the evidence suggests that all arrestins use similar mechanisms to achieve preferential binding to active phosphorylated GPCRs.
format	article
author	Preethi C. Karnam Sergey A. Vishnivetskiy Vsevolod V. Gurevich
author_facet	Preethi C. Karnam Sergey A. Vishnivetskiy Vsevolod V. Gurevich
author_sort	Preethi C. Karnam
title	Structural Basis of Arrestin Selectivity for Active Phosphorylated G Protein-Coupled Receptors
title_short	Structural Basis of Arrestin Selectivity for Active Phosphorylated G Protein-Coupled Receptors
title_full	Structural Basis of Arrestin Selectivity for Active Phosphorylated G Protein-Coupled Receptors
title_fullStr	Structural Basis of Arrestin Selectivity for Active Phosphorylated G Protein-Coupled Receptors
title_full_unstemmed	Structural Basis of Arrestin Selectivity for Active Phosphorylated G Protein-Coupled Receptors
title_sort	structural basis of arrestin selectivity for active phosphorylated g protein-coupled receptors
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3fcb56961cc14d2caef5ef0ab99655b7
work_keys_str_mv	AT preethickarnam structuralbasisofarrestinselectivityforactivephosphorylatedgproteincoupledreceptors AT sergeyavishnivetskiy structuralbasisofarrestinselectivityforactivephosphorylatedgproteincoupledreceptors AT vsevolodvgurevich structuralbasisofarrestinselectivityforactivephosphorylatedgproteincoupledreceptors
_version_	1718411796373569536

Structural Basis of Arrestin Selectivity for Active Phosphorylated G Protein-Coupled Receptors

Ejemplares similares