IFN alpha/beta binds to IFNAR2

Stable Identifier
R-HSA-909720
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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The ligand IFNalpha/beta (IFNA/B), interacts independently with the two interferon receptor subunits. Based on detailed binding studies with the extracellular domains of the receptor subunits tethered onto solid-supported membranes, a two-step binding mechanism was experimentally confirmed, where the ligand binds first to one of the receptor subunits and then recruits the second subunit (Gavutis et al. 2005). The efficiency of recruitment of the IFNA receptor subunits by the IFN ligand depends on the absolute and relative concentration of the receptor subunits.
IFNAR2 chain constitutively associates with JAK1 kinase in its cytoplasmic domain. In addition IFNAR2 also binds STAT2 in a constitutive manner and this interaction is biochemically different from the interaction of STAT2 with phosphorylated IFNAR1. Although this interaction facilitates the recruitment of STAT2 to the receptors, the biological significance of this constitutive STAT2 interaction to IFNAR2 remains unclear (Nguyen et al, 2002). IFNAR2 not only associates with STAT2, but also with STAT1 and this binding of STAT1 to IFNAR2 depends on the presence of STAT2 but not vice versa.
IFNA/B may first bind to the high-affinity subunit IFNAR2 and subsequently recruit IFNAR1 in a transient fashion (Lamken et al. 2004). Different type I IFNs interact differently with the two IFNA receptor (IFNAR) subunits, IFNB generates a more stable signaling complex than IFNA subtypes. The interaction between IFNalpha2 (IFNA2) and IFNAR2 has an affinity in the nM range, whereas the affinity of the interaction with INFB is about tenfold tighter.

Literature References
PubMed ID Title Journal Year
9334213 A region of the beta subunit of the interferon alpha receptor different from box 1 interacts with Jak1 and is sufficient to activate the Jak-Stat pathway and induce an antiviral state

Domanski, P, Fish, E, Nadeau, OW, Witte, M, Platanias, LC, Yan, H, Krolewski, J, Pitha, P, Colamonici, OR

J Biol Chem 1997
15778442 Lateral ligand-receptor interactions on membranes probed by simultaneous fluorescence-interference detection

Gavutis, M, Lata, S, Lamken, P, Müller, P, Piehler, J

Biophys J 2005
12842042 The human type I interferon receptor: NMR structure reveals the molecular basis of ligand binding

Chill, JH, Quadt, SR, Levy, R, Schreiber, G, Anglister, J

Structure 2003
9121453 Functional subdomains of STAT2 required for preassociation with the alpha interferon receptor and for signaling

Li, X, Leung, S, Kerr, IM, Stark, GR

Mol Cell Biol 1997
17969444 The receptor of the type I interferon family

Uzé, G, Schreiber, G, Piehler, J, Pellegrini, S

Curr Top Microbiol Immunol 2007
15312780 Ligand-induced assembling of the type I interferon receptor on supported lipid bilayers

Lamken, P, Lata, S, Gavutis, M, Piehler, J

J Mol Biol 2004
10395669 Determination of residues involved in ligand binding and signal transmission in the human IFN-alpha receptor 2

Chuntharapai, A, Gibbs, V, Lu, J, Ow, A, Marsters, S, Ashkenazi, A, De Vos, A, Jin Kim, K

J Immunol 1999
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