View source for 7xn6


==Cryo-EM structure of CopC-CaM-caspase-3 with ADPR-deacylization==
<StructureSection load='7xn6' size='340' side='right'caption='[[7xn6]], [[Resolution|resolution]] 3.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7xn6]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Chromobacterium_violaceum Chromobacterium violaceum] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XN6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XN6 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]] 3.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1LTQ:ADP-RIBOXANATED+ARGININE'>A1LTQ</scene>, <scene name='pdbligand=NCA:NICOTINAMIDE'>NCA</scene></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=7xn6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xn6 OCA], [https://pdbe.org/7xn6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xn6 RCSB], [https://www.ebi.ac.uk/pdbsum/7xn6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xn6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CASP3_HUMAN CASP3_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.<ref>PMID:7596430</ref> <ref>PMID:21357690</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Programmed cell death and caspase proteins play a pivotal role in host innate immune response combating pathogen infections. Blocking cell death is employed by many bacterial pathogens as a universal virulence strategy. CopC family type III effectors, including CopC from an environmental pathogen Chromobacterium violaceum, utilize calmodulin (CaM) as a co-factor to inactivate caspases by arginine ADPR deacylization. However, the molecular basis of the catalytic and substrate/co-factor binding mechanism is unknown. Here, we determine successive cryo-EM structures of CaM-CopC-caspase-3 ternary complex in pre-reaction, transition, and post-reaction states, which elucidate a multistep enzymatic mechanism of CopC-catalyzed ADPR deacylization. Moreover, we capture a snapshot of the detachment of modified caspase-3 from CopC. These structural insights are validated by mutagenesis analyses of CopC-mediated ADPR deacylization in vitro and animal infection in vivo. Our study offers a structural framework for understanding the molecular basis of arginine ADPR deacylization catalyzed by the CopC family.

Structural insights into caspase ADPR deacylization catalyzed by a bacterial effector and host calmodulin.,Zhang K, Peng T, Tao X, Tian M, Li Y, Wang Z, Ma S, Hu S, Pan X, Xue J, Luo J, Wu Q, Fu Y, Li S Mol Cell. 2022 Dec 15;82(24):4712-4726.e7. doi: 10.1016/j.molcel.2022.10.032. , Epub 2022 Nov 23. PMID:36423631<ref>PMID:36423631</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7xn6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Chromobacterium violaceum]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fu Y]]
[[Category: Hu SF]]
[[Category: Li S]]
[[Category: Li YX]]
[[Category: Luo JW]]
[[Category: Ma SF]]
[[Category: Pan X]]
[[Category: Peng T]]
[[Category: Tao XY]]
[[Category: Tian M]]
[[Category: Wang Z]]
[[Category: Wu QL]]
[[Category: Xue J]]
[[Category: Zhang K]]