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2h24

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(New page: 200px<br /> <applet load="2h24" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h24, resolution 2.0&Aring;" /> '''Crystal structure of...)
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[[Image:2h24.gif|left|200px]]<br />
 
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<applet load="2h24" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2h24, resolution 2.0&Aring;" />
 
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'''Crystal structure of human IL-10'''<br />
 
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==Overview==
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==Crystal structure of human IL-10==
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Interleukin-10 receptor 2 (IL-10R2) is a critical component of the, IL-10.IL-10R1.IL-10R2 complex which regulates IL-10-mediated, immunomodulatory responses. The ternary IL-10 signaling complex is, assembled in a sequential order with the IL-10.IL-10R1 interaction, occurring first followed by engagement of the IL-10R2 chain. In this study, we map the IL-10R2 binding site on IL-10 using surface plasmon resonance, and cell-based assays. Critical IL-10R2 binding residues are located in, helix A adjacent to the previously identified IL-10R1 recognition surface., Interestingly, IL-10R2 binding residues located in the N-terminal end of, helix A exhibit large structural differences between unbound cIL-10 and, cIL-10.IL-10R1 crystal structures. This suggests IL-10R1-induced, conformational changes regulate IL-10R2 binding and assembly of the, ternary IL-10.IL-10R1.IL-10R2 complex. The basic mechanistic features of, the assembly process are likely shared by six additional class-2 cytokines, (viral IL-10s, IL-22, IL-26, IL-28A, IL28B, and IL-29) to promote IL-10R2, binding to six additional receptor complexes. These studies highlight the, importance of structure in regulating low affinity protein-protein, interactions and IL-10 signal transduction.
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<StructureSection load='2h24' size='340' side='right'caption='[[2h24]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2h24]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H24 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H24 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2h24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h24 OCA], [https://pdbe.org/2h24 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h24 RCSB], [https://www.ebi.ac.uk/pdbsum/2h24 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h24 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/IL10_HUMAN IL10_HUMAN] Inhibits the synthesis of a number of cytokines, including IFN-gamma, IL-2, IL-3, TNF and GM-CSF produced by activated macrophages and by helper T-cells.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h2/2h24_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2h24 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Interleukin-10 receptor 2 (IL-10R2) is a critical component of the IL-10.IL-10R1.IL-10R2 complex which regulates IL-10-mediated immunomodulatory responses. The ternary IL-10 signaling complex is assembled in a sequential order with the IL-10.IL-10R1 interaction occurring first followed by engagement of the IL-10R2 chain. In this study we map the IL-10R2 binding site on IL-10 using surface plasmon resonance and cell-based assays. Critical IL-10R2 binding residues are located in helix A adjacent to the previously identified IL-10R1 recognition surface. Interestingly, IL-10R2 binding residues located in the N-terminal end of helix A exhibit large structural differences between unbound cIL-10 and cIL-10.IL-10R1 crystal structures. This suggests IL-10R1-induced conformational changes regulate IL-10R2 binding and assembly of the ternary IL-10.IL-10R1.IL-10R2 complex. The basic mechanistic features of the assembly process are likely shared by six additional class-2 cytokines (viral IL-10s, IL-22, IL-26, IL-28A, IL28B, and IL-29) to promote IL-10R2 binding to six additional receptor complexes. These studies highlight the importance of structure in regulating low affinity protein-protein interactions and IL-10 signal transduction.
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==Disease==
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Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex.,Yoon SI, Logsdon NJ, Sheikh F, Donnelly RP, Walter MR J Biol Chem. 2006 Nov 17;281(46):35088-96. Epub 2006 Sep 18. PMID:16982608<ref>PMID:16982608</ref>
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Known diseases associated with this structure: Graft-versus-host disease, protection against OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=124092 124092]], HIV-1, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=124092 124092]], Rheumatoid arthritis, progression of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=124092 124092]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2H24 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2H24 OCA].
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</div>
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<div class="pdbe-citations 2h24" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex., Yoon SI, Logsdon NJ, Sheikh F, Donnelly RP, Walter MR, J Biol Chem. 2006 Nov 17;281(46):35088-96. Epub 2006 Sep 18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16982608 16982608]
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*[[Interleukin 3D structures|Interleukin 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Walter, M.R.]]
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[[Category: Walter MR]]
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[[Category: Yoon, S.I.]]
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[[Category: Yoon SI]]
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[[Category: alpha-helix bundle]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:24:59 2007''
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Current revision

Crystal structure of human IL-10

PDB ID 2h24

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