4mix
PaToxG GlycosyltransferasePaToxG Glycosyltransferase
Structural highlights
FunctionPATOX_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 PubMedEntomopathogenic 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
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