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'''Unreleased structure'''


The entry 5t5w is ON HOLD until Paper Publication
==Structure of an affinity matured lambda-IFN/IFN-lambdaR1/IL-10Rbeta receptor complex==
 
<StructureSection load='5t5w' size='340' side='right' caption='[[5t5w]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
Authors:  
== Structural highlights ==
 
<table><tr><td colspan='2'>[[5t5w]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T5W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T5W FirstGlance]. <br>
Description:  
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
[[Category: Unreleased Structures]]
<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=5t5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t5w OCA], [http://pdbe.org/5t5w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t5w RCSB], [http://www.ebi.ac.uk/pdbsum/5t5w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t5w ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/I10R2_HUMAN I10R2_HUMAN]] Autosomal recessive early-onset inflammatory bowel disease. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/IFNL3_HUMAN IFNL3_HUMAN]] Response to antiviral treatment in hepatitis C. 
== Function ==
[[http://www.uniprot.org/uniprot/I10R2_HUMAN I10R2_HUMAN]] Shared cell surface receptor required for the activation of five class 2 cytokines: IL10, IL22, IL26, IL28, and IFNL1. The IFNLR1/IL10RB dimer is a receptor for the cytokine ligands IFNL2 and IFNL3 and mediates their antiviral activity. The ligand/receptor complex stimulate the activation of the JAK/STAT signaling pathway leading to the expression of IFN-stimulated genes (ISG), which contribute to the antiviral state.<ref>PMID:12469119</ref> <ref>PMID:15123776</ref>  [[http://www.uniprot.org/uniprot/IFNL3_HUMAN IFNL3_HUMAN]] Cytokine with antiviral, antitumour and immunomodulatory activities. Plays a critical role in the antiviral host defense, predominantly in the epithelial tissues. Acts as a ligand for the heterodimeric class II cytokine receptor composed of IL10RB and IFNLR1, and receptor engagement leads to the activation of the JAK/STAT signaling pathway resulting in the expression of IFN-stimulated genes (ISG), which mediate the antiviral state. Has a restricted receptor distribution and therefore restricted targets: is primarily active in epithelial cells and this cell type-selective action is because of the epithelial cell-specific expression of its receptor IFNLR1. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium. Exerts an immunomodulatory effect by up-regulating MHC class I antigen expression.<ref>PMID:12469119</ref> <ref>PMID:12483210</ref>  [[http://www.uniprot.org/uniprot/INLR1_HUMAN INLR1_HUMAN]] The IFNLR1/IL10RB dimer is a receptor for IFNL1, IFNL2 and IFNL3. The ligand/receptor complex seems to signal through the Jak-STAT pathway. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium.<ref>PMID:12521379</ref> <ref>PMID:12469119</ref> <ref>PMID:12483210</ref>  
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Garcia, K C]]
[[Category: Jude, K M]]
[[Category: Mendoza, J L]]
[[Category: Cytokine]]
[[Category: Cytokine-cytokine receptor complex]]
[[Category: Receptor]]

Revision as of 17:04, 29 March 2017

Structure of an affinity matured lambda-IFN/IFN-lambdaR1/IL-10Rbeta receptor complexStructure of an affinity matured lambda-IFN/IFN-lambdaR1/IL-10Rbeta receptor complex

Structural highlights

5t5w is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[I10R2_HUMAN] Autosomal recessive early-onset inflammatory bowel disease. The disease is caused by mutations affecting the gene represented in this entry. [IFNL3_HUMAN] Response to antiviral treatment in hepatitis C.

Function

[I10R2_HUMAN] Shared cell surface receptor required for the activation of five class 2 cytokines: IL10, IL22, IL26, IL28, and IFNL1. The IFNLR1/IL10RB dimer is a receptor for the cytokine ligands IFNL2 and IFNL3 and mediates their antiviral activity. The ligand/receptor complex stimulate the activation of the JAK/STAT signaling pathway leading to the expression of IFN-stimulated genes (ISG), which contribute to the antiviral state.[1] [2] [IFNL3_HUMAN] Cytokine with antiviral, antitumour and immunomodulatory activities. Plays a critical role in the antiviral host defense, predominantly in the epithelial tissues. Acts as a ligand for the heterodimeric class II cytokine receptor composed of IL10RB and IFNLR1, and receptor engagement leads to the activation of the JAK/STAT signaling pathway resulting in the expression of IFN-stimulated genes (ISG), which mediate the antiviral state. Has a restricted receptor distribution and therefore restricted targets: is primarily active in epithelial cells and this cell type-selective action is because of the epithelial cell-specific expression of its receptor IFNLR1. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium. Exerts an immunomodulatory effect by up-regulating MHC class I antigen expression.[3] [4] [INLR1_HUMAN] The IFNLR1/IL10RB dimer is a receptor for IFNL1, IFNL2 and IFNL3. The ligand/receptor complex seems to signal through the Jak-STAT pathway. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium.[5] [6] [7]

References

  1. ↑ Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol. 2003 Jan;4(1):63-8. Epub 2002 Dec 2. PMID:12469119 doi:10.1038/ni873
  2. ↑ Donnelly RP, Sheikh F, Kotenko SV, Dickensheets H. The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain. J Leukoc Biol. 2004 Aug;76(2):314-21. Epub 2004 May 3. PMID:15123776 doi:http://dx.doi.org/10.1189/jlb.0204117
  3. ↑ Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol. 2003 Jan;4(1):63-8. Epub 2002 Dec 2. PMID:12469119 doi:10.1038/ni873
  4. ↑ Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, Shah NK, Langer JA, Sheikh F, Dickensheets H, Donnelly RP. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol. 2003 Jan;4(1):69-77. Epub 2002 Dec 16. PMID:12483210 doi:10.1038/ni875
  5. ↑ Dumoutier L, Lejeune D, Hor S, Fickenscher H, Renauld JC. Cloning of a new type II cytokine receptor activating signal transducer and activator of transcription (STAT)1, STAT2 and STAT3. Biochem J. 2003 Mar 1;370(Pt 2):391-6. PMID:12521379 doi:10.1042/BJ20021935
  6. ↑ Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol. 2003 Jan;4(1):63-8. Epub 2002 Dec 2. PMID:12469119 doi:10.1038/ni873
  7. ↑ Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, Shah NK, Langer JA, Sheikh F, Dickensheets H, Donnelly RP. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol. 2003 Jan;4(1):69-77. Epub 2002 Dec 16. PMID:12483210 doi:10.1038/ni875

5t5w, resolution 2.85Å

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