NMR mapping of the IFNAR1-EC binding site on IFNα2 reveals allosteric changes in the IFNAR2-EC binding site

Autor(en): Akabayov, S.R.
Biron, Z.
Lamken, P.
Piehler, J. 
Anglister, J.
Stichwörter: Interferon-alpha; Receptor, Interferon alpha-beta, 156986-95-7; Allosteric communication; Binary complexes; Cell surface receptors; Cross peaks; Extracellular domains; Intracellular signals; NMR studies; Site directed mutagenesis; Type i interferons, Binding energy; Biochemistry; Complexation; Electric conductivity measurement; Enzyme activity; Nuclear magnetic resonance; Signal transduction, Binding sites, alpha2 interferon; interferon receptor, allosterism; article; binding site; controlled study; heteronuclear single quantum coherence; nuclear magnetic resonance; pH; priority journal; protein binding; protein interaction; site directed mutagenesis; spectrometer, Amino Acid Sequence; Binding Sites; Interferon-alpha; Kinetics; Models, Molecular; Nuclear Magnetic Resonance, Biomolecular; Protein Structure, Tertiary; Receptor, Interferon alpha-beta
Erscheinungsdatum: 2010
Journal: Biochemistry
Volumen: 49
Ausgabe: 4
Startseite: 687
Seitenende: 695
Zusammenfassung: 
All type I interferons (IFNs) bind to a common cell-surface receptor consisting of two subunits. IFNs initiate intracellular signal transduction cascades by simultaneous interaction with the extracellular domains of its receptor subunits, IFNAR1 and IFNAR2. In this study, we mapped the surface of IFNα2 interacting with the extracellular domain of IFNAR1 (IFNAR1-EC) by following changes in or the disappearance of the 1H- 15NTROSY-HSQC cross peaks of IFNα2 caused by the binding of the extracellular domain of IFNAR1 (IFNAR1-EC) to the binary complex of IFNα2 with IFNAR2-EC. The NMR study of the 89 kDa complex was conducted at pH 8 and 308 K using an 800 MHz spectrometer. IFNAR1 binding affected a total of 47 of 165 IFNα2 residues contained in two large patches on the face of the protein opposing the binding site for IFNAR2 and in a third patch located on the face containing the IFNAR2 binding site. The first two patches form the IFNAR1 binding site, and one of these matches the IFNAR1 binding site previously identified by site-directed mutagenesis. The third patch partially matches the IFNα2 binding site for IFNAR2-EC, indicating allosteric communication between the binding sites for the two receptor subunits. © 2010 American Chemical Society.
ISSN: 00062960
DOI: 10.1021/bi901313x
Externe URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-75149162520&doi=10.1021%2fbi901313x&partnerID=40&md5=ee8a11acd53f7f8159276f4f87919603

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