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6hv6

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Revision as of 09:30, 30 January 2019

Crystal structure of PatoxP, a cysteine protease-like domain of Photorhabdus asymbiotica toxin PaTox

Structural highlights

6hv6 is a 1 chain structure with sequence from Phoaa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	PAU_02230 (PHOAA)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

The nematode mutualistic bacterium Photorhabdus asymbiotica produces a large virulence-associated multifunctional protein toxin named PaTox. A glycosyltransferase domain and a deamidase domain of this large toxin function as effectors that specifically target host Rho GTPases and heterotrimeric G proteins, respectively. Modification of these intracellular regulators results in toxicity toward insects and mammalian cells. In this study, we identified a cysteine protease-like domain spanning PaTox residues 1844-2114 (PaTox(P)), upstream of these two effector domains and characterized by three conserved amino acid residues (Cys-1865, His-1955, and Asp-1975). We determined the crystal structure of the PaTox(P) C1865A variant by native single-wavelength anomalous diffraction of sulfur atoms (sulfur-SAD). At 2.0 A resolution, this structure revealed a catalytic site typical for papain-like cysteine proteases, comprising a catalytic triad, oxyanion hole, and typical secondary structural elements. The PaTox(P) structure had highest similarity to that of the AvrPphB protease from Pseudomonas syringae classified as a C58-protease. Furthermore, we observed that PaTox(P) shares structural homology also with non-C58-cysteine proteases, deubiquitinases, and deamidases. Upon delivery into insect larvae, PaTox(P) alone without full-length PaTox had no toxic effects. Yet, PaTox(P) expression in mammalian cells was toxic and enhanced the apoptotic phenotype induced by PaTox in HeLa cells. We propose that PaTox(P) is a C58-like cysteine protease module that is essential for full PaTox activity.

A cysteine protease-like domain enhances the cytotoxic effects of the Photorhabdus asymbiotica toxin PaTox.,Bogdanovic X, Schneider S, Levanova N, Wirth C, Trillhaase C, Steinemann M, Hunte C, Aktories K, Jank T J Biol Chem. 2018 Nov 26. pii: RA118.005043. doi: 10.1074/jbc.RA118.005043. PMID:30478175^[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
↑ Bogdanovic X, Schneider S, Levanova N, Wirth C, Trillhaase C, Steinemann M, Hunte C, Aktories K, Jank T. A cysteine protease-like domain enhances the cytotoxic effects of the Photorhabdus asymbiotica toxin PaTox. J Biol Chem. 2018 Nov 26. pii: RA118.005043. doi: 10.1074/jbc.RA118.005043. PMID:30478175 doi:http://dx.doi.org/10.1074/jbc.RA118.005043

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6hv6"

@@ Line 3: / Line 3: @@
 <StructureSection load='6hv6' size='340' side='right' caption='[[6hv6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6hv6]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HV6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HV6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6hv6]] is a 1 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=6HV6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HV6 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene></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=6hv6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hv6 OCA], [http://pdbe.org/6hv6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hv6 RCSB], [http://www.ebi.ac.uk/pdbsum/6hv6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hv6 ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Phoaa]]
 [[Category: Bogdanovic, X]]
 [[Category: Hunte, c]]

6hv6

From Proteopedia

Revision as of 09:30, 30 January 2019

Crystal structure of PatoxP, a cysteine protease-like domain of Photorhabdus asymbiotica toxin PaTox

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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