Cargando…

Binding of interferon reduces the force of unfolding for interferon receptor 1

Differential signaling of the type I interferon receptor (IFNAR) has been correlated with the ability of its subunit, IFNAR1, to differentially recognize a large spectrum of different ligands, which involves intricate conformational re-arrangements of multiple interacting domains. To shed light onto...

Descripción completa

Detalles Bibliográficos
Autores principales: Chuartzman, Silvia G., Nevo, Reinat, Waichman, Sharon, Shental, Dalit, Piehler, Jacob, Levy, Yaakov, Reich, Ziv, Kapon, Ruti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389645/
https://www.ncbi.nlm.nih.gov/pubmed/28403186
http://dx.doi.org/10.1371/journal.pone.0175413
_version_ 1782521312234700800
author Chuartzman, Silvia G.
Nevo, Reinat
Waichman, Sharon
Shental, Dalit
Piehler, Jacob
Levy, Yaakov
Reich, Ziv
Kapon, Ruti
author_facet Chuartzman, Silvia G.
Nevo, Reinat
Waichman, Sharon
Shental, Dalit
Piehler, Jacob
Levy, Yaakov
Reich, Ziv
Kapon, Ruti
author_sort Chuartzman, Silvia G.
collection PubMed
description Differential signaling of the type I interferon receptor (IFNAR) has been correlated with the ability of its subunit, IFNAR1, to differentially recognize a large spectrum of different ligands, which involves intricate conformational re-arrangements of multiple interacting domains. To shed light onto the structural determinants governing ligand recognition, we compared the force-induced unfolding of the IFNAR1 ectodomain when bound to interferon and when free, using the atomic force microscope and steered molecular dynamics simulations. Unexpectedly, we find that IFNAR1 is easier to mechanically unfold when bound to interferon than when free. Analysis of the structures indicated that the origin of the reduction in unfolding forces is a conformational change in IFNAR1 induced by ligand binding.
format Online
Article
Text
id pubmed-5389645
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-53896452017-05-03 Binding of interferon reduces the force of unfolding for interferon receptor 1 Chuartzman, Silvia G. Nevo, Reinat Waichman, Sharon Shental, Dalit Piehler, Jacob Levy, Yaakov Reich, Ziv Kapon, Ruti PLoS One Research Article Differential signaling of the type I interferon receptor (IFNAR) has been correlated with the ability of its subunit, IFNAR1, to differentially recognize a large spectrum of different ligands, which involves intricate conformational re-arrangements of multiple interacting domains. To shed light onto the structural determinants governing ligand recognition, we compared the force-induced unfolding of the IFNAR1 ectodomain when bound to interferon and when free, using the atomic force microscope and steered molecular dynamics simulations. Unexpectedly, we find that IFNAR1 is easier to mechanically unfold when bound to interferon than when free. Analysis of the structures indicated that the origin of the reduction in unfolding forces is a conformational change in IFNAR1 induced by ligand binding. Public Library of Science 2017-04-12 /pmc/articles/PMC5389645/ /pubmed/28403186 http://dx.doi.org/10.1371/journal.pone.0175413 Text en © 2017 Chuartzman et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Chuartzman, Silvia G.
Nevo, Reinat
Waichman, Sharon
Shental, Dalit
Piehler, Jacob
Levy, Yaakov
Reich, Ziv
Kapon, Ruti
Binding of interferon reduces the force of unfolding for interferon receptor 1
title Binding of interferon reduces the force of unfolding for interferon receptor 1
title_full Binding of interferon reduces the force of unfolding for interferon receptor 1
title_fullStr Binding of interferon reduces the force of unfolding for interferon receptor 1
title_full_unstemmed Binding of interferon reduces the force of unfolding for interferon receptor 1
title_short Binding of interferon reduces the force of unfolding for interferon receptor 1
title_sort binding of interferon reduces the force of unfolding for interferon receptor 1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389645/
https://www.ncbi.nlm.nih.gov/pubmed/28403186
http://dx.doi.org/10.1371/journal.pone.0175413
work_keys_str_mv AT chuartzmansilviag bindingofinterferonreducestheforceofunfoldingforinterferonreceptor1
AT nevoreinat bindingofinterferonreducestheforceofunfoldingforinterferonreceptor1
AT waichmansharon bindingofinterferonreducestheforceofunfoldingforinterferonreceptor1
AT shentaldalit bindingofinterferonreducestheforceofunfoldingforinterferonreceptor1
AT piehlerjacob bindingofinterferonreducestheforceofunfoldingforinterferonreceptor1
AT levyyaakov bindingofinterferonreducestheforceofunfoldingforinterferonreceptor1
AT reichziv bindingofinterferonreducestheforceofunfoldingforinterferonreceptor1
AT kaponruti bindingofinterferonreducestheforceofunfoldingforinterferonreceptor1