Identification of Critical Residues in Bovine IFNAR-1 Responsible for Interferon Binding

Ligand-induced Assembling of the Type I Interferon Receptor on Supported Lipid Bilayers

“…By using neutralizing antibodies, the binding site for IFNs on ifnar1 was mapped to the Ig-like domains 2 and 3 of ifnar1. 18 This observation was confirmed by several studies with bovine ifnar1, 19,20 which binds human IFNas with high affinity. These results indicated that the ligand binding site of ifnar1 does not correspond to a classical cytokine binding module.…”

Ligand Binding Induces a Conformational Change in ifnar1 that Is Propagated to Its Membrane-Proximal Domain

“…15,19,21 In contrast, the three N-terminal domains of ifnar1 are required for binding of IFNs, 22,23 yet ifnar1 binds IFN ligands with affinities that are 2-3 orders of magnitude lower than that of ifnar2. 24 Mutational studies have corroborated the involvement of the three N-terminal Ig-like domains of ifnar1 in the interaction with the ligand, 25,26 which was also confirmed by a recent three-dimensional reconstruction of the ternary complex by a single-particle electron microscopic analysis. 27 The membraneproximal Ig-like domain is not required for ligand binding, but has very specific properties required for the assembly of the ternary complex on the plasma membrane.…”

Differential Receptor Subunit Affinities of Type I Interferons Govern Differential Signal Activation

“…[16][17][18][19][20][21] While only minor differences were observed in the structure of the complexes of ifnar2-EC with IFNα2 and IFNβ, 22 a ten to 20-fold higher affinity of IFNβ for ifnar2-EC was observed. While the interaction of IFNs with the extracellular domain of ifnar1 (ifnar1-EC) appears rather complex, 23,24 competitive binding and largely overlapping binding epitopes were observed for IFNα2 and IFNβ. 25 These binding studies suggested that IFNα2 and IFNβ recruit a 1:1:1 complex with ifnar2 and ifnar1, which probably have rather similar architectures.…”