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[[Image:1lk3.jpg|left|200px]]<br /><applet load="1lk3" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1lk3, resolution 1.91&Aring;" />
'''ENGINEERED HUMAN INTERLEUKIN-10 MONOMER COMPLEXED TO 9D7 FAB FRAGMENT'''<br />


==Overview==
==ENGINEERED HUMAN INTERLEUKIN-10 MONOMER COMPLEXED TO 9D7 FAB FRAGMENT==
IL-10 is a dimeric cytokine that must engage its high-affinity cell surface receptor, IL-10R1, to induce multiple cellular activities. Here we report the 1.9 A crystal structure of an engineered IL-10 monomer (IL-10M1) in complex with a neutralizing Fab fragment (9D7Fab). 9D7Fab and IL-10R1 bind distinct nonoverlapping surfaces on IL-10M1. Antagonism of the IL-10M1/IL-10R1 interaction is the result of 9D7Fab-induced conformational changes in the CD loop of IL-10M1 that indirectly alter the structure of the IL-10R1 binding site. A single mutation (Ile87Ala) in the same CD loop region of the Epstein-Barr virus IL-10 (ebvIL-10) also reduces IL-10R1 binding affinity, suggesting that ebvIL-10 and 9D7Fab use similar allosteric mechanisms to modulate IL-10R1 affinity and biological activity.
<StructureSection load='1lk3' size='340' side='right'caption='[[1lk3]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1lk3]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LK3 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.91&#8491;</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=1lk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lk3 OCA], [https://pdbe.org/1lk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lk3 RCSB], [https://www.ebi.ac.uk/pdbsum/1lk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lk3 ProSAT]</span></td></tr>
</table>
== Function ==
[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.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lk/1lk3_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1lk3 ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
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]]
*[[Interleukin 3D structures|Interleukin 3D structures]]
 
__TOC__
==About this Structure==
</StructureSection>
1LK3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LK3 OCA].
 
==Reference==
Noncompetitive antibody neutralization of IL-10 revealed by protein engineering and x-ray crystallography., Josephson K, Jones BC, Walter LJ, DiGiacomo R, Indelicato SR, Walter MR, Structure. 2002 Jul;10(7):981-7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12121653 12121653]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Single protein]]
[[Category: DiGiacomo R]]
[[Category: DiGiacomo, R.]]
[[Category: Indelicato SR]]
[[Category: Indelicato, S R.]]
[[Category: Jones BC]]
[[Category: Jones, B C.]]
[[Category: Josephson K]]
[[Category: Josephson, K.]]
[[Category: Walter LJ]]
[[Category: Walter, L J.]]
[[Category: Walter MR]]
[[Category: Walter, M R.]]
[[Category: antigen-antibody complex]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:45:43 2008''

Latest revision as of 11:10, 3 April 2024

ENGINEERED HUMAN INTERLEUKIN-10 MONOMER COMPLEXED TO 9D7 FAB FRAGMENTENGINEERED HUMAN INTERLEUKIN-10 MONOMER COMPLEXED TO 9D7 FAB FRAGMENT

Structural highlights

1lk3 is a 6 chain structure with sequence from Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.91Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1lk3, resolution 1.91Å

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