1n6v: Difference between revisions
New page: left|200px<br /> <applet load="1n6v" size="450" color="white" frame="true" align="right" spinBox="true" caption="1n6v" /> '''Average structure of the interferon-binding... |
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'''Average structure of the interferon-binding ectodomain of the human type I interferon receptor'''<br /> | '''Average structure of the interferon-binding ectodomain of the human type I interferon receptor'''<br /> | ||
==Overview== | ==Overview== | ||
The potent antiviral and antiproliferative activities of human type I | 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. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1N6V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | 1N6V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N6V OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Anglister, J.]] | [[Category: Anglister, J.]] | ||
[[Category: Chill, J | [[Category: Chill, J H.]] | ||
[[Category: Levy, R.]] | [[Category: Levy, R.]] | ||
[[Category: Quadt, S | [[Category: Quadt, S R.]] | ||
[[Category: Schreiber, G.]] | [[Category: Schreiber, G.]] | ||
[[Category: fibronectin fold]] | [[Category: fibronectin fold]] | ||
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[[Category: two-domain structure]] | [[Category: two-domain structure]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:02:55 2008'' | ||
Revision as of 12:02, 21 February 2008
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Average structure of the interferon-binding ectodomain of the human type I interferon receptor
Overview
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.
Disease
Known disease associated with this structure: Hepatitis B virus, susceptibility to OMIM:[602376]
About this Structure
1N6V is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
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