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-\AA resolution represents a canonical GT-A fold and is the smallest glycosyltransferase toxin known. (1)H-NMR analysis identifies PaTox as a retaining glycosyltransferase. The glutamine-deamidase domain of PaTox blocks GTP hydrolysis of heterotrimeric G$\alpha$q/11 and G$\alpha$i proteins, thereby activating RhoA. Thus, PaTox hijacks host GTPase signaling in a bidirectional manner by deamidation-induced activation and glycosylation-induced inactivation of GTPases.
%0 Journal Article
%1 jankBacterialToxinCatalyzing2013
%A Jank, Thomas
%A Bogdanović, Xenia
%A Wirth, Christophe
%A Haaf, Erik
%A Spoerner, Michael
%A Böhmer, Kira E.
%A Steinemann, Marcus
%A Orth, Joachim H. C.
%A Kalbitzer, Hans Robert
%A Warscheid, Bettina
%A Hunte, Carola
%A Aktories, Klaus
%C United States
%D 2013
%J Nature structural & molecular biology
%K Acid Amino Conformation,rho Data,Photorhabdus/*enzymology,Protein Diphosphate GTP-Binding Molecular,Molecular N-Acetylglucosamine/*chemistry/*metabolism Proteins/*metabolism,to_read,Tyrosine/*metabolism,Uridine Resonance Sequence Sequence,Animals,Bacterial Spectroscopy,Models Toxins/*chemistry/*metabolism,Crystallography X-Ray,Glycosylation,Humans,Magnetic
%N 11
%P 1273--1280
%R 10.1038/nsmb.2688
%T A Bacterial Toxin Catalyzing Tyrosine Glycosylation of Rho and Deamidation of Gq and Gi Proteins.
%V 20
%X 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-\AA resolution represents a canonical GT-A fold and is the smallest glycosyltransferase toxin known. (1)H-NMR analysis identifies PaTox as a retaining glycosyltransferase. The glutamine-deamidase domain of PaTox blocks GTP hydrolysis of heterotrimeric G$\alpha$q/11 and G$\alpha$i proteins, thereby activating RhoA. Thus, PaTox hijacks host GTPase signaling in a bidirectional manner by deamidation-induced activation and glycosylation-induced inactivation of GTPases.
@article{jankBacterialToxinCatalyzing2013,
abstract = {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-{\AA} resolution represents a canonical GT-A fold and is the smallest glycosyltransferase toxin known. (1)H-NMR analysis identifies PaTox as a retaining glycosyltransferase. The glutamine-deamidase domain of PaTox blocks GTP hydrolysis of heterotrimeric G{$\alpha$}q/11 and G{$\alpha$}i proteins, thereby activating RhoA. Thus, PaTox hijacks host GTPase signaling in a bidirectional manner by deamidation-induced activation and glycosylation-induced inactivation of GTPases.},
added-at = {2024-05-17T13:01:35.000+0200},
address = {United States},
author = {Jank, Thomas and Bogdanovi{\'c}, Xenia and Wirth, Christophe and Haaf, Erik and Spoerner, Michael and B{\"o}hmer, Kira E. and Steinemann, Marcus and Orth, Joachim H. C. and Kalbitzer, Hans Robert and Warscheid, Bettina and Hunte, Carola and Aktories, Klaus},
biburl = {https://www.bibsonomy.org/bibtex/2f8dcae2f450e4e96c41b401f2bc7208b/warscheidlab},
doi = {10.1038/nsmb.2688},
interhash = {e899a326726b33a1ca52db86b9812ae0},
intrahash = {f8dcae2f450e4e96c41b401f2bc7208b},
issn = {1545-9985},
journal = {Nature structural \& molecular biology},
keywords = {Acid Amino Conformation,rho Data,Photorhabdus/*enzymology,Protein Diphosphate GTP-Binding Molecular,Molecular N-Acetylglucosamine/*chemistry/*metabolism Proteins/*metabolism,to_read,Tyrosine/*metabolism,Uridine Resonance Sequence Sequence,Animals,Bacterial Spectroscopy,Models Toxins/*chemistry/*metabolism,Crystallography X-Ray,Glycosylation,Humans,Magnetic},
langid = {english},
month = nov,
number = 11,
pages = {1273--1280},
pmid = {24141704},
timestamp = {2024-05-17T13:01:35.000+0200},
title = {A Bacterial Toxin Catalyzing Tyrosine Glycosylation of {{Rho}} and Deamidation of {{Gq}} and {{Gi}} Proteins.},
volume = 20,
year = 2013
}