7pqe
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Structure of SidJ/CaM bound to SdeA in post-catalysis state== |
| - | <StructureSection load='7pqe' size='340' side='right'caption='[[7pqe]]' scene=''> | + | <StructureSection load='7pqe' size='340' side='right'caption='[[7pqe]], [[Resolution|resolution]] 3.70Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7pqe]] is a 3 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=7PQE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PQE FirstGlance]. <br> |
| - | </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=7pqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pqe OCA], [https://pdbe.org/7pqe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pqe RCSB], [https://www.ebi.ac.uk/pdbsum/7pqe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pqe ProSAT]</span></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]] 3.7Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7pqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pqe OCA], [https://pdbe.org/7pqe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pqe RCSB], [https://www.ebi.ac.uk/pdbsum/7pqe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pqe ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == 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:31330531, PubMed:31330532). In turn, inhibits SdeA ubiquitinating activity. Glutamylates also related SdeB, SdeC and SidE (PubMed:31123136, PubMed:31330531). Glutamylase activity only occurs in the host since it requires host calmodulin (PubMed:28497808, PubMed:31123136, PubMed:31330531, PubMed:31330532). 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 == | ||
| + | Legionella pneumophila (LP) avoids phagocytosis by secreting nearly 300 effector proteins into the host cytosol. SidE family of effectors (SdeA, SdeB, SdeC and SidE) employ phosphoribosyl ubiquitination to target multiple host Rab GTPases and innate immune factors. To suppress the deleterious toxicity of SidE enzymes in a timely manner, LP employs a metaeffector named SidJ. Upon activation by host Calmodulin (CaM), SidJ executes an ATP-dependent glutamylation to modify the catalytic residue Glu860 in the mono-ADP-ribosyl transferase (mART) domain of SdeA. SidJ is a unique glutamylase that adopts a kinase-like fold but contains two nucleotide-binding pockets. There is a lack of consensus about the substrate recognition and catalytic mechanism of SidJ. Here, we determined the cryo-EM structure of SidJ in complex with its substrate SdeA in two different states of catalysis. Our structures reveal that both phosphodiesterase (PDE) and mART domains of SdeA make extensive contacts with SidJ. In the pre-glutamylation state structure of the SidJ-SdeA complex, adenylylated E860 of SdeA is inserted into the non-canonical (migrated) nucleotide-binding pocket of SidJ. Structure-based mutational analysis indicates that SidJ employs its migrated pocket for the glutamylation of SdeA. Finally, using mass spectrometry, we identified several transient autoAMPylation sites close to both the catalytic pockets of SidJ. Our data provide unique insights into the substrate recognition and the mechanism of protein glutamylation by the pseudokinase SidJ. | ||
| + | |||
| + | Structural basis for protein glutamylation by the Legionella pseudokinase SidJ.,Adams M, Sharma R, Colby T, Weis F, Matic I, Bhogaraju S Nat Commun. 2021 Oct 26;12(1):6174. doi: 10.1038/s41467-021-26429-y. PMID:34702826<ref>PMID:34702826</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7pqe" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Calmodulin 3D structures|Calmodulin 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Legionella pneumophila]] |
| + | [[Category: Adams M]] | ||
| + | [[Category: Bhogaraju S]] | ||
Current revision
Structure of SidJ/CaM bound to SdeA in post-catalysis state
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