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'''SOLUTION STRUCTURE OF ICEBERG, AN INHIBITOR OF INTERLEUKIN-1BETA GENERATION'''<br />


==Overview==
==SOLUTION STRUCTURE OF ICEBERG, AN INHIBITOR OF INTERLEUKIN-1BETA GENERATION==
ProIL-1beta is a proinflammatory cytokine that is proteolytically, processed to its active form by caspase-1. Upon receipt of a, proinflammatory stimulus, an upstream adaptor, RIP2, binds and, oligomerizes caspase-1 zymogen, promoting its autoactivation. ICEBERG is a, novel protein that inhibits generation of IL-1beta by interacting with, caspase-1 and preventing its association with RIP2. ICEBERG is induced by, proinflammatory stimuli, suggesting that it may be part of a negative, feedback loop. Consistent with this, enforced retroviral expression of, ICEBERG inhibits lipopolysaccharide-induced IL-1beta generation. The, structure of ICEBERG reveals it to be a member of the death-domain-fold, superfamily. The distribution of surface charge is complementary to the, homologous prodomain of caspase-1, suggesting that charge-charge, interactions mediate binding of ICEBERG to the prodomain of caspase-1.
<StructureSection load='1dgn' size='340' side='right'caption='[[1dgn]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1dgn]] 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=1DGN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DGN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1dgn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dgn OCA], [https://pdbe.org/1dgn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dgn RCSB], [https://www.ebi.ac.uk/pdbsum/1dgn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dgn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CAR18_HUMAN CAR18_HUMAN] Inhibits generation of IL-1-beta by interacting with caspase-1 and preventing its association with RIP2. Down-regulates the release of IL1B.<ref>PMID:11051551</ref>
== 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/dg/1dgn_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=1dgn ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ProIL-1beta is a proinflammatory cytokine that is proteolytically processed to its active form by caspase-1. Upon receipt of a proinflammatory stimulus, an upstream adaptor, RIP2, binds and oligomerizes caspase-1 zymogen, promoting its autoactivation. ICEBERG is a novel protein that inhibits generation of IL-1beta by interacting with caspase-1 and preventing its association with RIP2. ICEBERG is induced by proinflammatory stimuli, suggesting that it may be part of a negative feedback loop. Consistent with this, enforced retroviral expression of ICEBERG inhibits lipopolysaccharide-induced IL-1beta generation. The structure of ICEBERG reveals it to be a member of the death-domain-fold superfamily. The distribution of surface charge is complementary to the homologous prodomain of caspase-1, suggesting that charge-charge interactions mediate binding of ICEBERG to the prodomain of caspase-1.


==About this Structure==
ICEBERG: a novel inhibitor of interleukin-1beta generation.,Humke EW, Shriver SK, Starovasnik MA, Fairbrother WJ, Dixit VM Cell. 2000 Sep 29;103(1):99-111. PMID:11051551<ref>PMID:11051551</ref>
1DGN 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=1DGN OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
ICEBERG: a novel inhibitor of interleukin-1beta generation., Humke EW, Shriver SK, Starovasnik MA, Fairbrother WJ, Dixit VM, Cell. 2000 Sep 29;103(1):99-111. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11051551 11051551]
</div>
<div class="pdbe-citations 1dgn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Dixit, V.M.]]
[[Category: Dixit VM]]
[[Category: Fairbrother, W.J.]]
[[Category: Fairbrother WJ]]
[[Category: Humke, E.W.]]
[[Category: Humke EW]]
[[Category: Shriver, S.K.]]
[[Category: Shriver SK]]
[[Category: Starovasnik, M.A.]]
[[Category: Starovasnik MA]]
[[Category: antiparallel six-helix bundle]]
[[Category: greek-key]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:32:26 2007''

Latest revision as of 08:24, 22 May 2024

SOLUTION STRUCTURE OF ICEBERG, AN INHIBITOR OF INTERLEUKIN-1BETA GENERATION

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