The G protein coupled receptor CXCR4 designed by the QTY code becomes more hydrophilic and retains cell signaling activity

Abstract G protein-coupled receptors (GPCRs) are vital for diverse biological functions, including vision, smell, and aging. They are involved in a wide range of diseases, and are among the most important targets of medicinal drugs. Tools that facilitate GPCR studies or GPCR-based technologies or th...

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Autores principales:	Lotta Tegler, Karolina Corin, Horst Pick, Jennifer Brookes, Michael Skuhersky, Horst Vogel, Shuguang Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d25ff2f655d440be8967bb59115106d6
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spelling	oai:doaj.org-article:d25ff2f655d440be8967bb59115106d62021-12-02T16:08:58ZThe G protein coupled receptor CXCR4 designed by the QTY code becomes more hydrophilic and retains cell signaling activity10.1038/s41598-020-77659-x2045-2322https://doaj.org/article/d25ff2f655d440be8967bb59115106d62020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77659-xhttps://doaj.org/toc/2045-2322Abstract G protein-coupled receptors (GPCRs) are vital for diverse biological functions, including vision, smell, and aging. They are involved in a wide range of diseases, and are among the most important targets of medicinal drugs. Tools that facilitate GPCR studies or GPCR-based technologies or therapies are thus critical to develop. Here we report using our QTY (glutamine, threonine, tyrosine) code to systematically replace 29 membrane-facing leucine, isoleucine, valine, and phenylalanine residues in the transmembrane α-helices of the GPCR CXCR4. This variant, CXCR4QTY29, became more hydrophilic, while retaining the ability to bind its ligand CXCL12. When transfected into HEK293 cells, it inserted into the cell membrane, and initiated cellular signaling. This QTY code has the potential to improve GPCR and membrane protein studies by making it possible to design functional hydrophilic receptors. This tool can be applied to diverse α-helical membrane proteins, and may aid in the development of other applications, including clinical therapies.Lotta TeglerKarolina CorinHorst PickJennifer BrookesMichael SkuherskyHorst VogelShuguang ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lotta Tegler Karolina Corin Horst Pick Jennifer Brookes Michael Skuhersky Horst Vogel Shuguang Zhang The G protein coupled receptor CXCR4 designed by the QTY code becomes more hydrophilic and retains cell signaling activity
description	Abstract G protein-coupled receptors (GPCRs) are vital for diverse biological functions, including vision, smell, and aging. They are involved in a wide range of diseases, and are among the most important targets of medicinal drugs. Tools that facilitate GPCR studies or GPCR-based technologies or therapies are thus critical to develop. Here we report using our QTY (glutamine, threonine, tyrosine) code to systematically replace 29 membrane-facing leucine, isoleucine, valine, and phenylalanine residues in the transmembrane α-helices of the GPCR CXCR4. This variant, CXCR4QTY29, became more hydrophilic, while retaining the ability to bind its ligand CXCL12. When transfected into HEK293 cells, it inserted into the cell membrane, and initiated cellular signaling. This QTY code has the potential to improve GPCR and membrane protein studies by making it possible to design functional hydrophilic receptors. This tool can be applied to diverse α-helical membrane proteins, and may aid in the development of other applications, including clinical therapies.
format	article
author	Lotta Tegler Karolina Corin Horst Pick Jennifer Brookes Michael Skuhersky Horst Vogel Shuguang Zhang
author_facet	Lotta Tegler Karolina Corin Horst Pick Jennifer Brookes Michael Skuhersky Horst Vogel Shuguang Zhang
author_sort	Lotta Tegler
title	The G protein coupled receptor CXCR4 designed by the QTY code becomes more hydrophilic and retains cell signaling activity
title_short	The G protein coupled receptor CXCR4 designed by the QTY code becomes more hydrophilic and retains cell signaling activity
title_full	The G protein coupled receptor CXCR4 designed by the QTY code becomes more hydrophilic and retains cell signaling activity
title_fullStr	The G protein coupled receptor CXCR4 designed by the QTY code becomes more hydrophilic and retains cell signaling activity
title_full_unstemmed	The G protein coupled receptor CXCR4 designed by the QTY code becomes more hydrophilic and retains cell signaling activity
title_sort	g protein coupled receptor cxcr4 designed by the qty code becomes more hydrophilic and retains cell signaling activity
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/d25ff2f655d440be8967bb59115106d6
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The G protein coupled receptor CXCR4 designed by the QTY code becomes more hydrophilic and retains cell signaling activity

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