The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties

Abstract IL-17A and IL-17F are prominent members of the IL-17 family of cytokines that regulates both innate and adaptive immunity. IL-17A has been implicated in chronic inflammatory and autoimmune diseases, and anti-IL-17A antibodies have shown remarkable clinical efficacy in psoriasis and psoriati...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Arnaud Goepfert, Sylvie Lehmann, Emmanuelle Wirth, Jean-Michel Rondeau
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/62586932f66c4a62852c9be2789af9d4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:62586932f66c4a62852c9be2789af9d4
record_format	dspace
spelling	oai:doaj.org-article:62586932f66c4a62852c9be2789af9d42021-12-02T15:05:27ZThe human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties10.1038/s41598-017-08360-92045-2322https://doaj.org/article/62586932f66c4a62852c9be2789af9d42017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08360-9https://doaj.org/toc/2045-2322Abstract IL-17A and IL-17F are prominent members of the IL-17 family of cytokines that regulates both innate and adaptive immunity. IL-17A has been implicated in chronic inflammatory and autoimmune diseases, and anti-IL-17A antibodies have shown remarkable clinical efficacy in psoriasis and psoriatic arthritis patients. IL-17A and IL-17F are homodimeric cytokines that can also form the IL-17A/F heterodimer whose precise role in health and disease remains elusive. All three cytokines signal through the assembly of a ternary complex with the IL-17RA and IL-17RC receptors. Here we report the X-ray analysis of the human IL-17A/F heterodimer that reveals a two-faced cytokine closely mimicking IL-17A as well as IL-17F. We also present the crystal structure of its complex with the IL-17RA receptor. Unexpectedly in view of the much higher affinity of this receptor toward IL-17A, we find that IL-17RA is bound to the “F-face” of the heterodimer in the crystal. Using site-directed mutagenesis, we then demonstrate that IL-17RA can also bind to the “A-face” of IL-17A/F with similar affinity. Further, we show that IL-17RC does not discriminate between the two faces of the cytokine heterodimer either, thus enabling the formation of two topologically-distinct heterotrimeric complexes with potentially different signaling properties.Arnaud GoepfertSylvie LehmannEmmanuelle WirthJean-Michel RondeauNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Arnaud Goepfert Sylvie Lehmann Emmanuelle Wirth Jean-Michel Rondeau The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties
description	Abstract IL-17A and IL-17F are prominent members of the IL-17 family of cytokines that regulates both innate and adaptive immunity. IL-17A has been implicated in chronic inflammatory and autoimmune diseases, and anti-IL-17A antibodies have shown remarkable clinical efficacy in psoriasis and psoriatic arthritis patients. IL-17A and IL-17F are homodimeric cytokines that can also form the IL-17A/F heterodimer whose precise role in health and disease remains elusive. All three cytokines signal through the assembly of a ternary complex with the IL-17RA and IL-17RC receptors. Here we report the X-ray analysis of the human IL-17A/F heterodimer that reveals a two-faced cytokine closely mimicking IL-17A as well as IL-17F. We also present the crystal structure of its complex with the IL-17RA receptor. Unexpectedly in view of the much higher affinity of this receptor toward IL-17A, we find that IL-17RA is bound to the “F-face” of the heterodimer in the crystal. Using site-directed mutagenesis, we then demonstrate that IL-17RA can also bind to the “A-face” of IL-17A/F with similar affinity. Further, we show that IL-17RC does not discriminate between the two faces of the cytokine heterodimer either, thus enabling the formation of two topologically-distinct heterotrimeric complexes with potentially different signaling properties.
format	article
author	Arnaud Goepfert Sylvie Lehmann Emmanuelle Wirth Jean-Michel Rondeau
author_facet	Arnaud Goepfert Sylvie Lehmann Emmanuelle Wirth Jean-Michel Rondeau
author_sort	Arnaud Goepfert
title	The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties
title_short	The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties
title_full	The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties
title_fullStr	The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties
title_full_unstemmed	The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties
title_sort	human il-17a/f heterodimer: a two-faced cytokine with unique receptor recognition properties
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/62586932f66c4a62852c9be2789af9d4
work_keys_str_mv	AT arnaudgoepfert thehumanil17afheterodimeratwofacedcytokinewithuniquereceptorrecognitionproperties AT sylvielehmann thehumanil17afheterodimeratwofacedcytokinewithuniquereceptorrecognitionproperties AT emmanuellewirth thehumanil17afheterodimeratwofacedcytokinewithuniquereceptorrecognitionproperties AT jeanmichelrondeau thehumanil17afheterodimeratwofacedcytokinewithuniquereceptorrecognitionproperties AT arnaudgoepfert humanil17afheterodimeratwofacedcytokinewithuniquereceptorrecognitionproperties AT sylvielehmann humanil17afheterodimeratwofacedcytokinewithuniquereceptorrecognitionproperties AT emmanuellewirth humanil17afheterodimeratwofacedcytokinewithuniquereceptorrecognitionproperties AT jeanmichelrondeau humanil17afheterodimeratwofacedcytokinewithuniquereceptorrecognitionproperties
_version_	1718388833644445696

The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties

Ejemplares similares