Gln 63 of Rho is deamidated by Escherichia coli cytotoxic necrotizing factor-1
Abstract
The actin cytoskeleton is regulated by GTP-hydrolysing proteins, the Rho GTPases, which act as molecular switches in diverse signal-transduction processes. Various bacterial toxins can inactivate Rho GTPases by ADP-ribosylation or glucosylation. Previous research has identified Rho proteins as putative targets for Escherichia coli cytotoxic necrotizing factors 1 and 2 (CNF1 and 2). These toxins induce actin assembly and multinucleation in culture cells. Here we show that treatment of RhoA with CNF1 inhibits the intrinsic GTPase activity of RhoA and completely blocks GTPase activity stimulated by the Rho-GTPase-activating protein (rhoGAP). Analysis by mass spectrometry and amino-acid sequencing of proteolytic peptides derived from CNF1-treated RhoA indicate that CNF1 induces deamidation of a glutamine residue at position 63 (Gln 63) to give constitutively active Rho protein.
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Transglutamination of the Gln63 residue abolishes the intrinsic and GAP-stimulated GTPase activity of RhoA, leading to its permanent activation.
“Finally, various types of transglutamination of the Gln63 residue have been found to abolish the intrinsic and GAP-stimulated GTPase activity of RhoA, leading to its permanent activation [74,75,76].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [74]
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- Authors
- Schmidt, G., Sehr, P., Wilm, M., Selzer, J., Mann, M., & Aktories, K.
- Affiliations
- University of Freiburg (DE)
- European Molecular Biology Laboratory (DE)
- Corresponding author
- Aktories, Klaus
- Venue
- Nature
- Published
- 1997-06-12
- Volume
- 387
- Issue
- 6634
- Pages
- 725-729
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1647404354
- Cited by
- 530
- References
- 0
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 11 · 2023: 6 · 2022: 14 · 2021: 23 · 2020: 14 · 2019: 11 · 2018: 19 · 2017: 17 · 2016: 23 · 2015: 20 · 2014: 22 · 2013: 19 · 2012: 18
- FWCI
- 10.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- RhoA, cytotoxic necrotizing factor 1, deamidation, Rho GTPases, GTPase activity, RhoGAP, bacterial toxins, actin cytoskeleton, multinucleation
- MeSH terms
- Actins, Adenosine Diphosphate Ribose, Amino Acid Sequence, Animals, Bacterial Toxins, Cytoskeleton, Cytotoxins, Electrophoresis, Polyacrylamide Gel, Escherichia coli, Glutamine, Glycosylation, Guanosine Triphosphate, Microinjections, Molecular Sequence Data, Molecular Weight, Recombinant Fusion Proteins, Mass Spectrometry, 3T3 Cells, GTP-Binding Proteins, GTP Phosphohydrolases, GTPase-Activating Proteins, rhoA GTP-Binding Protein, Escherichia coli Proteins, Mice, ortho-Aminobenzoates
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