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| | ==Average structure of the interferon-binding ectodomain of the human type I interferon receptor== | | ==Average structure of the interferon-binding ectodomain of the human type I interferon receptor== |
| - | <StructureSection load='1n6v' size='340' side='right'caption='[[1n6v]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='1n6v' size='340' side='right'caption='[[1n6v]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1n6v]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N6V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1N6V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1n6v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N6V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N6V FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1n6u|1n6u]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 1 model</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1n6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n6v OCA], [http://pdbe.org/1n6v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1n6v RCSB], [http://www.ebi.ac.uk/pdbsum/1n6v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1n6v ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1n6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n6v OCA], [https://pdbe.org/1n6v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n6v RCSB], [https://www.ebi.ac.uk/pdbsum/1n6v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n6v ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/INAR2_HUMAN INAR2_HUMAN]] Associates with IFNAR1 to form the type I interferon receptor. Receptor for interferons alpha and beta. Involved in IFN-mediated STAT1, STAT2 and STAT3 activation. Isoform 1 and isoform 2 are directly involved in signal transduction due to their association with the TYR kinase, JAK1. Isoform 3 is a potent inhibitor of type I IFN receptor activity.<ref>PMID:8181059</ref> <ref>PMID:7665574</ref> <ref>PMID:7759950</ref> <ref>PMID:11682488</ref> <ref>PMID:12105218</ref> | + | [https://www.uniprot.org/uniprot/INAR2_HUMAN INAR2_HUMAN] Associates with IFNAR1 to form the type I interferon receptor. Receptor for interferons alpha and beta. Involved in IFN-mediated STAT1, STAT2 and STAT3 activation. Isoform 1 and isoform 2 are directly involved in signal transduction due to their association with the TYR kinase, JAK1. Isoform 3 is a potent inhibitor of type I IFN receptor activity.<ref>PMID:8181059</ref> <ref>PMID:7665574</ref> <ref>PMID:7759950</ref> <ref>PMID:11682488</ref> <ref>PMID:12105218</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n6/1n6v_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n6/1n6v_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Anglister, J]] | + | [[Category: Anglister J]] |
| - | [[Category: Chill, J H]] | + | [[Category: Chill JH]] |
| - | [[Category: Levy, R]] | + | [[Category: Levy R]] |
| - | [[Category: Quadt, S R]] | + | [[Category: Quadt SR]] |
| - | [[Category: Schreiber, G]] | + | [[Category: Schreiber G]] |
| - | [[Category: Fibronectin fold]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Immunoglobulin fold]]
| + | |
| - | [[Category: Two-domain structure]]
| + | |
| Structural highlights
Function
INAR2_HUMAN Associates with IFNAR1 to form the type I interferon receptor. Receptor for interferons alpha and beta. Involved in IFN-mediated STAT1, STAT2 and STAT3 activation. Isoform 1 and isoform 2 are directly involved in signal transduction due to their association with the TYR kinase, JAK1. Isoform 3 is a potent inhibitor of type I IFN receptor activity.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Novick D, Cohen B, Rubinstein M. The human interferon alpha/beta receptor: characterization and molecular cloning. Cell. 1994 May 6;77(3):391-400. PMID:8181059
- ↑ Domanski P, Witte M, Kellum M, Rubinstein M, Hackett R, Pitha P, Colamonici OR. Cloning and expression of a long form of the beta subunit of the interferon alpha beta receptor that is required for signaling. J Biol Chem. 1995 Sep 15;270(37):21606-11. PMID:7665574
- ↑ Novick D, Cohen B, Tal N, Rubinstein M. Soluble and membrane-anchored forms of the human IFN-alpha/beta receptor. J Leukoc Biol. 1995 May;57(5):712-8. PMID:7759950
- ↑ Wagner TC, Velichko S, Vogel D, Rani MR, Leung S, Ransohoff RM, Stark GR, Perez HD, Croze E. Interferon signaling is dependent on specific tyrosines located within the intracellular domain of IFNAR2c. Expression of IFNAR2c tyrosine mutants in U5A cells. J Biol Chem. 2002 Jan 11;277(2):1493-9. Epub 2001 Oct 26. PMID:11682488 doi:10.1074/jbc.M108928200
- ↑ Velichko S, Wagner TC, Turkson J, Jove R, Croze E. STAT3 activation by type I interferons is dependent on specific tyrosines located in the cytoplasmic domain of interferon receptor chain 2c. Activation of multiple STATS proceeds through the redundant usage of two tyrosine residues. J Biol Chem. 2002 Sep 20;277(38):35635-41. Epub 2002 Jun 24. PMID:12105218 doi:10.1074/jbc.M204578200
- ↑ 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
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