Intracellular plasma membrane guidance of Photorhabdus asymbiotica toxin is crucial for cell toxicity

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Thomas JankKlaus Aktories

Abstract

The bacterial toxin Photorhabdus asymbiotica toxin (PaTox) modifies Rho proteins by tyrosine GlcNAcylation and heterotrimeric Gα proteins by deamidation. Inactivation of Rho proteins results in F-actin disassembly in host cells. Here, we analyzed the subcellular distribution of PaTox and show that the glycosyltransferase domain of PaTox associates with the negatively charged inner surface of the plasma membrane. Localization studies with site-directed mutants, liposome precipitation analysis, lipid overlay assays, and confocal time-lapse microscopy revealed that a patch of positively charged lysine and arginine residues located on helix α1 of the glycosyltransferase is essential for membrane attachment. Using a helix1 deletion mutant, we show that plasma membrane localization of PaTox is essential for cytotoxicity and proved this by substitution of helix1 by an N-terminal myristoylation signal peptide, which restored plasma membrane localization and cytotoxicity. Furthermore, we also show that the intracellular deamidase activity of PaTox depends on the presence of the membrane localization domain. Comparison of PaTox membrane-binding domain with the 4-helix-bundle membrane-binding domain of Pasteurella multocida toxin, Vibrio ...Continue Reading

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Citations

Oct 8, 2015·Cellular Microbiology·Thomas JankKlaus Aktories
Jun 1, 2015·Toxicon : Official Journal of the International Society on Toxinology·Thomas JankKlaus Aktories
Mar 27, 2020·Microbiology·David J Clarke

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