6s5t

From Proteopedia

(Difference between revisions)

Current revision

Legionella pneumophila SidJ-Human calmodulin complex

6s5t, resolution 4.15Å

Structural highlights

6s5t is a 2 chain structure with sequence from Homo sapiens and Legionella pneumophila. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.15Å
Ligands:
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).^[1] ^[2] ^[3] ^[4]

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.

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Qiu J, Yu K, Fei X, Liu Y, Nakayasu ES, Piehowski PD, Shaw JB, Puvar K, Das C, Liu X, Luo ZQ. A unique deubiquitinase that deconjugates phosphoribosyl-linked protein ubiquitination. Cell Res. 2017 Jul;27(7):865-881. PMID:28497808 doi:10.1038/cr.2017.66
↑ Black MH, Osinski A, Gradowski M, Servage KA, Pawlowski K, Tomchick DR, Tagliabracci VS. Bacterial pseudokinase catalyzes protein polyglutamylation to inhibit the SidE-family ubiquitin ligases. Science. 2019 May 24;364(6442):787-792. doi: 10.1126/science.aaw7446. PMID:31123136 doi:http://dx.doi.org/10.1126/science.aaw7446
↑ Gan N, Zhen X, Liu Y, Xu X, He C, Qiu J, Liu Y, Fujimoto GM, Nakayasu ES, Zhou B, Zhao L, Puvar K, Das C, Ouyang S, Luo ZQ. Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase. Nature. 2019 Jul 22. pii: 10.1038/s41586-019-1439-1. doi:, 10.1038/s41586-019-1439-1. PMID:31330531 doi:http://dx.doi.org/10.1038/s41586-019-1439-1
↑ Bhogaraju S, Bonn F, Mukherjee R, Adams M, Pfleiderer MM, Galej WP, Matkovic V, Lopez-Mosqueda J, Kalayil S, Shin D, Dikic I. Inhibition of bacterial ubiquitin ligases by SidJ-calmodulin-catalysed glutamylation. Nature. 2019 Jul 22. pii: 10.1038/s41586-019-1440-8. doi:, 10.1038/s41586-019-1440-8. PMID:31330532 doi:http://dx.doi.org/10.1038/s41586-019-1440-8
↑ Bhogaraju S, Bonn F, Mukherjee R, Adams M, Pfleiderer MM, Galej WP, Matkovic V, Lopez-Mosqueda J, Kalayil S, Shin D, Dikic I. Inhibition of bacterial ubiquitin ligases by SidJ-calmodulin-catalysed glutamylation. Nature. 2019 Jul 22. pii: 10.1038/s41586-019-1440-8. doi:, 10.1038/s41586-019-1440-8. PMID:31330532 doi:http://dx.doi.org/10.1038/s41586-019-1440-8

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6s5t"

@@ Line 3: / Line 3: @@
 <SX load='6s5t' size='340' side='right' viewer='molstar' caption='[[6s5t]], [[Resolution|resolution]] 4.15&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6s5t]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_33152 Atcc 33152] and [http://en.wikipedia.org/wiki/Human Human]. 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 [http://proteopedia.org/fgij/fg.htm?mol=6S5T FirstGlance]. <br>
+<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" id="ligandDat"><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]] 4.15&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lpg2155 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=446 ATCC 33152]), CALM2, CAM2, CAMB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<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'>[http://proteopedia.org/fgij/fg.htm?mol=6s5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s5t OCA], [http://pdbe.org/6s5t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s5t RCSB], [http://www.ebi.ac.uk/pdbsum/6s5t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s5t ProSAT]</span></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>
-== 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 ==
-[[http://www.uniprot.org/uniprot/CALM2_HUMAN CALM2_HUMAN]] Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).<ref>PMID:16760425</ref> <ref>PMID:26969752</ref> <ref>PMID:27165696</ref>
+[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 ==
@@ Line 21: / Line 19: @@
 </div>
 <div class="pdbe-citations 6s5t" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Calmodulin 3D structures|Calmodulin 3D structures]]
 == References ==
 <references/>
 __TOC__
 </SX>
-[[Category: Atcc 33152]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Adams, M]]
+[[Category: Legionella pneumophila]]
-[[Category: Bhogaraju, S]]
+[[Category: Adams M]]
-[[Category: Galej, W P]]
+[[Category: Bhogaraju S]]
-[[Category: Pfleiderer, M M]]
+[[Category: Galej WP]]
-[[Category: Bacterial glutamylase]]
+[[Category: Pfleiderer MM]]
-[[Category: Calmodulin-dependent]]
-[[Category: Legionella]]
-[[Category: Pseudo kinase]]
-[[Category: Sdea]]
-[[Category: Serine ubiquitination]]
-[[Category: Sidj]]
-[[Category: Transferase]]

6s5t

From Proteopedia

Current revision

Legionella pneumophila SidJ-Human calmodulin complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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