1N6U

NMR structure of the interferon-binding ectodomain of the human interferon receptor

Summary for 1N6U

• Entry DOI: 10.2210/pdb1n6u/pdb
• NMR Information: BMRB: 5049
• Descriptor: Interferon-alpha/beta receptor beta chain (1 entity in total)
• Functional Keywords: immunoglobulin fold, fibronectin fold, two-domain structure, immune system
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 1: Membrane; Single-pass type I membrane protein. Isoform 2: Membrane; Single-pass type I membrane protein. Isoform 3: Secreted: P48551
• Total number of polymer chains: 1
• Total formula weight: 24323.44

Authors

Chill, J.H.,Quadt, S.R.,Levy, R.,Schreiber, G.,Anglister, J. (deposition date: 2002-11-12, release date: 2003-07-15, Last modification date: 2024-10-30)

Primary citation

Chill, J.H.,Quadt, S.R.,Levy, R.,Schreiber, G.,Anglister, J.
The human type I interferon receptor. NMR structure reveals the molecular basis of ligand binding.
Structure, 11:791-802, 2003

PubMed Abstract: 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.

PubMed: 12842042
DOI: 10.1016/S0969-2126(03)00120-5

Experimental method

SOLUTION NMR