title: A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation of Gq and Gi proteins.
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-Å 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 Gαq/11 and Gαi proteins, thereby activating RhoA. Thus, PaTox hijacks host GTPase signaling in a bidirectional manner by deamidation-induced activation and glycosylation-induced inactivation of GTPases.
authors.affiliation: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jank
authors.forename: Xenia
authors.initials: X
authors.lastname: Bogdanović
authors.forename: Christophe
authors.initials: C
authors.lastname: Wirth
authors.forename: Erik
authors.initials: E
authors.lastname: Haaf
authors.forename: Michael
authors.initials: M
authors.lastname: Spoerner
authors.forename: Kira E
authors.initials: KE
authors.lastname: Böhmer
authors.forename: Marcus
authors.initials: M
authors.lastname: Steinemann
authors.forename: Joachim H C
authors.initials: JH
authors.lastname: Orth
authors.forename: Hans Robert
authors.identifier: 0000000265142355
authors.initials: HR
authors.lastname: Kalbitzer
authors.forename: Bettina
authors.initials: B
authors.lastname: Warscheid
authors.forename: Carola
authors.initials: C
authors.lastname: Hunte
authors.forename: Klaus
authors.initials: K
authors.lastname: Aktories
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006031:Glycosylation; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020637:Photorhabdus / Q000201:enzymology*; D011487:Protein Conformation; D014443:Tyrosine / Q000378:metabolism*; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000737:chemistry* / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D014443:Tyrosine; D014537:Uridine Diphosphate N-Acetylglucosamine; D020741:rho GTP-Binding Proteins