5t5w: Difference between revisions

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<StructureSection load='5t5w' size='340' side='right'caption='[[5t5w]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
<StructureSection load='5t5w' size='340' side='right'caption='[[5t5w]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5t5w]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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>
<table><tr><td colspan='2'>[[5t5w]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. 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 [https://proteopedia.org/fgij/fg.htm?mol=5T5W FirstGlance]. <br>
</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>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL10RB, CRFB4, D21S58, D21S66 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IFNLR1, IL28RA, LICR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IFNL3, IL28B, IL28C, ZCYTO22 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL10RB, CRFB4, D21S58, D21S66 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IFNLR1, IL28RA, LICR2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IFNL3, IL28B, IL28C, ZCYTO22 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5t5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t5w OCA], [https://pdbe.org/5t5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5t5w RCSB], [https://www.ebi.ac.uk/pdbsum/5t5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5t5w ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== 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.   
[[https://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. [[https://www.uniprot.org/uniprot/IFNL3_HUMAN IFNL3_HUMAN]] Response to antiviral treatment in hepatitis C.   
== Function ==
== 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>   
[[https://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>  [[https://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>  [[https://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>   
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==

Revision as of 09:45, 24 March 2021

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 with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:IL10RB, CRFB4, D21S58, D21S66 (HUMAN), IFNLR1, IL28RA, LICR2 (HUMAN), IFNL3, IL28B, IL28C, ZCYTO22 (HUMAN)
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]

Publication Abstract from PubMed

Type III interferons (IFN-lambdas) signal through a heterodimeric receptor complex composed of the IFN-lambdaR1 subunit, specific for IFN-lambdas, and interleukin-10Rbeta (IL-10Rbeta), which is shared by multiple cytokines in the IL-10 superfamily. Low affinity of IL-10Rbeta for cytokines has impeded efforts aimed at crystallizing cytokine-receptor complexes. We used yeast surface display to engineer a higher-affinity IFN-lambda variant, H11, which enabled crystallization of the ternary complex. The structure revealed that IL-10Rbeta uses a network of tyrosine residues as hydrophobic anchor points to engage IL-10 family cytokines that present complementary hydrophobic binding patches, explaining its role as both a cross-reactive but cytokine-specific receptor. H11 elicited increased anti-proliferative and antiviral activities in vitro and in vivo. In contrast, engineered higher-affinity type I IFNs did not increase antiviral potency over wild-type type I IFNs. Our findings provide insight into cytokine recognition by the IL-10R family and highlight the plasticity of type III interferon signaling and its therapeutic potential.

The IFN-lambda-IFN-lambdaR1-IL-10Rbeta Complex Reveals Structural Features Underlying Type III IFN Functional Plasticity.,Mendoza JL, Schneider WM, Hoffmann HH, Vercauteren K, Jude KM, Xiong A, Moraga I, Horton TM, Glenn JS, de Jong YP, Rice CM, Garcia KC Immunity. 2017 Mar 21;46(3):379-392. doi: 10.1016/j.immuni.2017.02.017. PMID:28329704[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

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
  8. ↑ Mendoza JL, Schneider WM, Hoffmann HH, Vercauteren K, Jude KM, Xiong A, Moraga I, Horton TM, Glenn JS, de Jong YP, Rice CM, Garcia KC. The IFN-lambda-IFN-lambdaR1-IL-10Rbeta Complex Reveals Structural Features Underlying Type III IFN Functional Plasticity. Immunity. 2017 Mar 21;46(3):379-392. doi: 10.1016/j.immuni.2017.02.017. PMID:28329704 doi:http://dx.doi.org/10.1016/j.immuni.2017.02.017

5t5w, resolution 2.85Å

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