8sv1
From Proteopedia
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== Function == | == 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> | [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. | ||
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| + | 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> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8sv1" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Caspase-1 complex with interleukin-18
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Categories: Homo sapiens | Large Structures | Dong Y | Jon K | Pascal D | Wu H
