6s5t
From Proteopedia
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==Legionella pneumophila SidJ-Human calmodulin complex== | ==Legionella pneumophila SidJ-Human calmodulin complex== | ||
| - | < | + | <SX load='6s5t' size='340' side='right' viewer='molstar' caption='[[6s5t]], [[Resolution|resolution]] 4.15Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6s5t]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S5T OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6s5t]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Legionella_pneumophila Legionella pneumophila]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S5T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6S5T FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.15Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</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=6s5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s5t OCA], [https://pdbe.org/6s5t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6s5t RCSB], [https://www.ebi.ac.uk/pdbsum/6s5t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6s5t ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | == Disease == | ||
| - | [[http://www.uniprot.org/uniprot/CALM2_HUMAN CALM2_HUMAN]] Catecholaminergic polymorphic ventricular tachycardia;Brugada syndrome;Romano-Ward syndrome. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM2 are the cause of LQT15. | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/SIDJ_LEGPH SIDJ_LEGPH] Glutamylase that mediates the covalent attachment of glutamate moieties to SdeA on one of the catalytic residues that is required for its mono-ADP-ribosyltransferase activity (PubMed:31330532, PubMed:31330531). In turn, inhibits SdeA ubiquitinating activity. Glutamylates also related SdeB, SdeC and SidE (PubMed:31330531, PubMed:31123136). Glutamylase activity only occurs in the host since it requires host calmodulin (PubMed:28497808, PubMed:31330532, PubMed:31330531, PubMed:31123136). May also reverse the SdeA-mediated substrate ubiquitination by cleaving the phosphodiester bond that links phosphoribosylated ubiquitin to protein substrates via its deubiquitinase activity (PubMed:28497808).<ref>PMID:28497808</ref> <ref>PMID:31123136</ref> <ref>PMID:31330531</ref> <ref>PMID:31330532</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The family of bacterial SidE enzymes catalyses phosphoribosyl-linked (PR) serine ubiquitination and promotes infectivity of Legionella pneumophilia, a pathogenic bacterium causing Legionnaires' disease(1-3). SidEs share the genetic locus with the Legionella effector SidJ that spatiotemporally opposes their toxicity in yeast and mammalian cells, through an unknown mechanism(4-6). Deletion of SidJ leads to a significant defect in the growth of Legionella in both its natural host amoeba and in murine macrophages(4,5). Here, we demonstrate that SidJ is a glutamylase that modifies the catalytic glutamate in the mono-ADPribosyl transferase (mART) domain of SdeA thus blocking its ubiquitin (Ub) ligase activity. SidJ glutamylation activity requires interaction with calmodulin (CaM), a eukaryotic specific co-factor, and can be regulated by intracellular changes in Ca(2+) concentrations. The cryo-EM structure of SidJ/human apo-CaM complex revealed the architecture of this unique heterodimeric glutamylase. In infected cells, we show that SidJ mediates glutamylation of SidEs on the surface of Legionella-containing vacuoles (LCVs). Using quantitative proteomics, we also uncovered multiple host proteins as putative targets of SidJ-mediated glutamylation. Collectively, this study reveals the mechanism of SidE ligases inhibition by a SidJ/CaM glutamylase and opens new avenues for studying protein glutamylation, an understudied protein modification in higher eukaryotes. | ||
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| + | Inhibition of bacterial ubiquitin ligases by SidJ-calmodulin-catalysed glutamylation.,Bhogaraju S, Bonn F, Mukherjee R, Adams M, Pfleiderer MM, Galej WP, Matkovic V, Lopez-Mosqueda J, Kalayil S, Shin D, Dikic I Nature. 2019 Jul 22. pii: 10.1038/s41586-019-1440-8. doi:, 10.1038/s41586-019-1440-8. PMID:31330532<ref>PMID:31330532</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6s5t" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Calmodulin 3D structures|Calmodulin 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
| - | </ | + | </SX> |
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Legionella pneumophila]] |
| - | [[Category: | + | [[Category: Adams M]] |
| - | + | [[Category: Bhogaraju S]] | |
| - | + | [[Category: Galej WP]] | |
| - | [[Category: | + | [[Category: Pfleiderer MM]] |
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Current revision
Legionella pneumophila SidJ-Human calmodulin complex
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