View source for 8sv1


==Caspase-1 complex with interleukin-18==
<StructureSection load='8sv1' size='340' side='right'caption='[[8sv1]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8sv1]] is a 6 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=8SV1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SV1 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.5&#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=8sv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sv1 OCA], [https://pdbe.org/8sv1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sv1 RCSB], [https://www.ebi.ac.uk/pdbsum/8sv1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sv1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CASP1_HUMAN CASP1_HUMAN] Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis.<ref>PMID:7876192</ref> <ref>PMID:15498465</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Several interleukin-1 (IL-1) family members, including IL-1beta and IL-18, require processing by inflammasome-associated caspases to unleash their activities. Here, we unveil, by cryoelectron microscopy (cryo-EM), two major conformations of the complex between caspase-1 and pro-IL-18. One conformation is similar to the complex of caspase-4 and pro-IL-18, with interactions at both the active site and an exosite (closed conformation), and the other only contains interactions at the active site (open conformation). Thus, pro-IL-18 recruitment and processing by caspase-1 is less dependent on the exosite than the active site, unlike caspase-4. Structure determination by nuclear magnetic resonance uncovers a compact fold of apo pro-IL-18, which is similar to caspase-1-bound pro-IL-18 but distinct from cleaved IL-18. Binding sites for IL-18 receptor and IL-18 binding protein are only formed upon conformational changes after pro-IL-18 cleavage. These studies show how pro-IL-18 is selected as a caspase-1 substrate, and why cleavage is necessary for its inflammatory activity.

Structural transitions enable interleukin-18 maturation and signaling.,Dong Y, Bonin JP, Devant P, Liang Z, Sever AIM, Mintseris J, Aramini JM, Du G, Gygi SP, Kagan JC, Kay LE, Wu H Immunity. 2024 May 8:S1074-7613(24)00220-6. doi: 10.1016/j.immuni.2024.04.015. PMID:38733997<ref>PMID:38733997</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8sv1" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Dong Y]]
[[Category: Jon K]]
[[Category: Pascal D]]
[[Category: Wu H]]