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| | ==PaToxG Glycosyltransferase== | | ==PaToxG Glycosyltransferase== |
| - | <StructureSection load='4mix' size='340' side='right' caption='[[4mix]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='4mix' size='340' side='right'caption='[[4mix]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4mix]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Phoaa Phoaa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MIX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MIX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4mix]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Photorhabdus_asymbiotica_subsp._asymbiotica_ATCC_43949 Photorhabdus asymbiotica subsp. asymbiotica ATCC 43949]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MIX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MIX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</scene></td></tr> | + | </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=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=4mix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mix OCA], [https://pdbe.org/4mix PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mix RCSB], [https://www.ebi.ac.uk/pdbsum/4mix PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mix ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PAU_02230 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=553480 PHOAA])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mix OCA], [http://pdbe.org/4mix PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mix RCSB], [http://www.ebi.ac.uk/pdbsum/4mix PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mix ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PATOX_PHOAA PATOX_PHOAA] Toxin that acts on host cells by modifying Rho proteins by tyrosine GlcNAcylation and heterotrimeric G alpha proteins by deamidation. Catalyzes the mono-O-GlcNAcylation of small GTPases of the Rho family (RhoA, RhoB, RhoC, Rac1, Rac2, Rac3, Cdc42) in eukaryotic host cells at the conserved tyrosine residue located in the switch I region (Tyr-32/34), using UDP-N-acetylglucosamine (UDP-GlcNAc) as the sugar donor; other GTPases of the Rho, Ras or Rab families are not substrates. Tyrosine glycosylation inhibits Rho activation and prevents interaction with downstream effectors, resulting in actin disassembly, inhibition of phagocytosis, cell rounding, and toxicity toward insects and mammalian cells. Also catalyzes the deamidation of the catalytic glutamine in heterotrimeric G alpha proteins (Gi, Gq/11), which blocks GTP hydrolysis and arrests the G proteins in a permanent active state leading to activation of Rho GTPases. Thus, PaTox hijacks host GTPase signaling in a bidirectional manner by deamidation-induced activation and glycosylation-induced inactivation of GTPases.<ref>PMID:24141704</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Phoaa]] | + | [[Category: Large Structures]] |
| - | [[Category: Bogdanovic, X]] | + | [[Category: Photorhabdus asymbiotica subsp. asymbiotica ATCC 43949]] |
| - | [[Category: Hunte, C]] | + | [[Category: Bogdanovic X]] |
| - | [[Category: Wirth, C]] | + | [[Category: Hunte C]] |
| - | [[Category: Glycosyltransferase]] | + | [[Category: Wirth C]] |
| - | [[Category: Nucleotide-binding domain a/b/a]]
| + | |
| - | [[Category: Rho-protein]]
| + | |
| - | [[Category: Rossmann-like]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Tyrosine glycosylation]]
| + | |
| - | [[Category: Udp-glcnac]]
| + | |
| Structural highlights
Function
PATOX_PHOAA Toxin that acts on host cells by modifying Rho proteins by tyrosine GlcNAcylation and heterotrimeric G alpha proteins by deamidation. Catalyzes the mono-O-GlcNAcylation of small GTPases of the Rho family (RhoA, RhoB, RhoC, Rac1, Rac2, Rac3, Cdc42) in eukaryotic host cells at the conserved tyrosine residue located in the switch I region (Tyr-32/34), using UDP-N-acetylglucosamine (UDP-GlcNAc) as the sugar donor; other GTPases of the Rho, Ras or Rab families are not substrates. Tyrosine glycosylation inhibits Rho activation and prevents interaction with downstream effectors, resulting in actin disassembly, inhibition of phagocytosis, cell rounding, and toxicity toward insects and mammalian cells. Also catalyzes the deamidation of the catalytic glutamine in heterotrimeric G alpha proteins (Gi, Gq/11), which blocks GTP hydrolysis and arrests the G proteins in a permanent active state leading to activation of Rho GTPases. Thus, PaTox hijacks host GTPase signaling in a bidirectional manner by deamidation-induced activation and glycosylation-induced inactivation of GTPases.[1]
Publication Abstract from PubMed
Entomopathogenic Photorhabdus asymbiotica is an emerging pathogen in humans. Here, we identified a P. asymbiotica protein toxin (PaTox), which contains a glycosyltransferase and a deamidase domain. PaTox mono-O-glycosylates Y32 (or Y34) of eukaryotic Rho GTPases by using UDP-N-acetylglucosamine (UDP-GlcNAc). Tyrosine glycosylation inhibits Rho activation and prevents interaction with downstream effectors, resulting in actin disassembly, inhibition of phagocytosis and toxicity toward insects and mammalian cells. The crystal structure of the PaTox glycosyltransferase domain in complex with UDP-GlcNAc determined at 1.8-A resolution represents a canonical GT-A fold and is the smallest glycosyltransferase toxin known. 1H-NMR analysis identifies PaTox as a retaining glycosyltransferase. The glutamine-deamidase domain of PaTox blocks GTP hydrolysis of heterotrimeric Galphaq/11 and Galphai proteins, thereby activating RhoA. Thus, PaTox hijacks host GTPase signaling in a bidirectional manner by deamidation-induced activation and glycosylation-induced inactivation of GTPases.
A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation of G and G proteins.,Jank T, Bogdanovic X, Wirth C, Haaf E, Spoerner M, Bohmer KE, Steinemann M, Orth JH, Kalbitzer HR, Warscheid B, Hunte C, Aktories K Nat Struct Mol Biol. 2013 Oct 20. doi: 10.1038/nsmb.2688. PMID:24141704[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jank T, Bogdanovic X, Wirth C, Haaf E, Spoerner M, Bohmer KE, Steinemann M, Orth JH, Kalbitzer HR, Warscheid B, Hunte C, Aktories K. A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation of G and G proteins. Nat Struct Mol Biol. 2013 Oct 20. doi: 10.1038/nsmb.2688. PMID:24141704 doi:http://dx.doi.org/10.1038/nsmb.2688
- ↑ Jank T, Bogdanovic X, Wirth C, Haaf E, Spoerner M, Bohmer KE, Steinemann M, Orth JH, Kalbitzer HR, Warscheid B, Hunte C, Aktories K. A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation of G and G proteins. Nat Struct Mol Biol. 2013 Oct 20. doi: 10.1038/nsmb.2688. PMID:24141704 doi:http://dx.doi.org/10.1038/nsmb.2688
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