Structural highlights
Publication Abstract from 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. 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[1]
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
