title: Binding of interferon reduces the force of unfolding for interferon receptor 1.
abstract: 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.
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Chuartzman
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Reinat
authors.initials: R
authors.lastname: Nevo
authors.affiliation: Department of Biology, University of Osnabrück, Osnabrück, Germany.
authors.forename: Sharon
authors.initials: S
authors.lastname: Waichman
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Dalit
authors.initials: D
authors.lastname: Shental
authors.affiliation: Department of Biology, University of Osnabrück, Osnabrück, Germany.
authors.forename: Jacob
authors.initials: J
authors.lastname: Piehler
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Levy
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Reich
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ruti
authors.identifier: http://orcid.org/0000-0002-0618-6470
authors.initials: R
authors.lastname: Kapon
mesh_terms: D006801:Humans; D007370:Interferon Type I / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D058767:Protein Unfolding; D053633:Receptor, Interferon alpha-beta / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D007370:Interferon Type I; D053633:Receptor, Interferon alpha-beta