A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation of Gq and Gi proteins.

Article Details


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 Gq and Gi proteins.

Nat Struct Mol Biol. 2013 Nov;20(11):1273-80. doi: 10.1038/nsmb.2688. Epub 2013 Oct 20.

PubMed ID
24141704 [ View in 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. (1)H-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.

DrugBank Data that Cites this Article

NameUniProt ID
Ras-related C3 botulinum toxin substrate 1P63000Details
Transforming protein RhoAP61586Details
Rho-related GTP-binding protein RhoBP62745Details
Guanine nucleotide-binding protein G(i) subunit alpha-1P63096Details
Cell division control protein 42 homologP60953Details
Ras-related C3 botulinum toxin substrate 2P15153Details