NMR structure of the interferon-binding ectodomain of the human interferon receptor
Publication Abstract from PubMed
The potent antiviral and antiproliferative activities of human type I interferons (IFNs) are mediated by a single receptor comprising two subunits, IFNAR1 and IFNAR2. The structure of the IFNAR2 IFN binding ectodomain (IFNAR2-EC), the first helical cytokine receptor structure determined in solution, reveals the molecular basis for IFN binding. The atypical perpendicular orientation of its two fibronectin domains explains the lack of C domain involvement in ligand binding. A model of the IFNAR2-EC/IFNalpha2 complex based on double mutant cycle-derived constraints uncovers an extensive and predominantly aliphatic hydrophobic patch on the receptor that interacts with a matching hydrophobic surface of IFNalpha2. An adjacent motif of alternating charged side chains guides the two proteins into a tight complex. The binding interface may account for crossreactivity and ligand specificity of the receptor. This molecular description of IFN binding should be invaluable for study and design of IFN-based biomedical agents.
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 Jul;11(7):791-802. PMID:12842042
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1n6u is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA.
- Chill JH, Quadt SR, Levy R, Schreiber G, Anglister J. The human type I interferon receptor: NMR structure reveals the molecular basis of ligand binding. Structure. 2003 Jul;11(7):791-802. PMID:12842042
- Thomas C, Moraga I, Levin D, Krutzik PO, Podoplelova Y, Trejo A, Lee C, Yarden G, Vleck SE, Glenn JS, Nolan GP, Piehler J, Schreiber G, Garcia KC. Structural Linkage between Ligand Discrimination and Receptor Activation by Type I Interferons. Cell. 2011 Aug 19;146(4):621-32. PMID:21854986 doi:10.1016/j.cell.2011.06.048