6kn0: Difference between revisions

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-'''Unreleased structure'''
-The entry 6kn0 is ON HOLD  until Paper Publication
+==caspase-1 P20/P10 C285A in complex with human GSDMD-C domain==
+<StructureSection load='6kn0' size='340' side='right'caption='[[6kn0]], [[Resolution|resolution]] 2.79&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6kn0]] 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=6KN0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KN0 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]] 2.793&#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=6kn0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kn0 OCA], [https://pdbe.org/6kn0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kn0 RCSB], [https://www.ebi.ac.uk/pdbsum/6kn0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kn0 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 ==
+The pyroptosis execution protein GSDMD is cleaved by inflammasome-activated caspase-1 and LPS-activated caspase-11/4/5. The cleavage unmasks the pore-forming domain from GSDMD-C-terminal domain. How the caspases recognize GSDMD and its connection with caspase activation are unknown. Here, we show site-specific caspase-4/11 autoprocessing, generating a p10 product, is required and sufficient for cleaving GSDMD and inducing pyroptosis. The p10-form autoprocessed caspase-4/11 binds the GSDMD-C domain with a high affinity. Structural comparison of autoprocessed and unprocessed capase-11 identifies a beta sheet induced by the autoprocessing. In caspase-4/11-GSDMD-C complex crystal structures, the beta sheet organizes a hydrophobic GSDMD-binding interface that is only possible for p10-form caspase-4/11. The binding promotes dimerization-mediated caspase activation, rendering a cleavage independently of the cleavage-site tetrapeptide sequence. Crystal structure of caspase-1-GSDMD-C complex shows a similar GSDMD-recognition mode. Our study reveals an unprecedented substrate-targeting mechanism for caspases. The hydrophobic interface suggests an additional space for developing inhibitors specific for pyroptotic caspases.
-Authors:
+Structural Mechanism for GSDMD Targeting by Autoprocessed Caspases in Pyroptosis.,Wang K, Sun Q, Zhong X, Zeng M, Zeng H, Shi X, Li Z, Wang Y, Zhao Q, Shao F, Ding J Cell. 2020 Mar 5;180(5):941-955.e20. doi: 10.1016/j.cell.2020.02.002. Epub 2020, Feb 27. PMID:32109412<ref>PMID:32109412</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6kn0" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Caspase 3D structures|Caspase 3D structures]]
+*[[Gasdermin 3D structures|Gasdermin 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Ding J]]
+[[Category: Sun Q]]