Gln 63 of Rho is deamidated by Escherichia coli cytotoxic necrotizing factor-1

Schmidt, Gudula; Sehr, Peter; Wilm, Matthias; Selzer, Jörg; Mann, Matthias; Aktories, Klaus

doi:10.1038/42735

Cited by 508 publications

(487 citation statements)

References 22 publications

Supporting

Mentioning

466

Contrasting

Unclassified

Order By: Relevance

“…CheD is structurally related to the cytotoxic necrotizing factor family of bacterial deamidases (44,45). Deamidation is a posttranslational modification used by multiple bacterial virulence factors to modify the function of eukaryotic host target proteins (39).…”

Section: Evidence For Three Gene-duplication Events In Hopaf1 Evolutimentioning

confidence: 99%

Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction

Washington

Mukhtar

Finkel

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

HopAF1 is a type III effector protein of unknown function encoded in the genomes of several strains of Pseudomonas syringae and other plant pathogens. Structural modeling predicted that HopAF1 is closely related to deamidase proteins. Deamidation is the irreversible substitution of an amide group with a carboxylate group. Several bacterial virulence factors are deamidases that manipulate the activity of specific host protein substrates. We identified Arabidopsis methylthioadenosine nucleosidase proteins MTN1 and MTN2 as putative targets of HopAF1 deamidation. MTNs are enzymes in the Yang cycle, which is essential for the high levels of ethylene biosynthesis in Arabidopsis. We hypothesized that HopAF1 inhibits the host defense response by manipulating MTN activity and consequently ethylene levels. We determined that bacterially delivered HopAF1 inhibits ethylene biosynthesis induced by pathogenassociated molecular patterns and that Arabidopsis mtn1 mtn2 mutant plants phenocopy the effect of HopAF1. Furthermore, we identified two conserved asparagines in MTN1 and MTN2 from Arabidopsis that confer loss of function phenotypes when deamidated via site-specific mutation. These residues are potential targets of HopAF1 deamidation. HopAF1-mediated manipulation of Yang cycle MTN proteins is likely an evolutionarily conserved mechanism whereby HopAF1 orthologs from multiple plant pathogens contribute to disease in a large variety of plant hosts.

show abstract

Section: Evidence For Three Gene-duplication Events In Hopaf1 Evolutimentioning

confidence: 99%

Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction

Washington

Mukhtar

Finkel

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Binding of ADP-ribosylated RhoA to GDI is increased, which leads to a cytosolic accumulation of inactive RhoRhoGDI complex ("trapping effect") Studies from recent years identified Rho GTPases as the preferred targets of several bacterial toxins. In addition to the ADP-ribosylation by C3, Rho GTPases are covalently modified by glucosylation (e.g., by clostridial glucosylating toxins; Aktories and Barbieri 2005;Just et al 1995b;Aktories and Just 2005;Voth and Ballard 2005;Just and Gerhard 2004), deamidation (e.g., by E. coli cytotoxic necrotizing factor; Schmidt et al 1997;Flatau et al 1997), and transglutamination (Bordetella dermonecrotizing factor; Masuda et al 2000) resulting in inactivation or activation of the GTPases respectively (Fig. 2).…”

Section: The Targets Of C3-like Exoenzymes Are Molecular Switchesmentioning

confidence: 99%

C3 exoenzymes, novel insights into structure and action of Rho-ADP-ribosylating toxins

Vogelsgesang

Pautsch

Aktories

2006

Naunyn-Schmied Arch Pharmacol

Self Cite

102

View full text Add to dashboard Cite

The family of C3-like exoenzymes comprises seven bacterial ADP-ribosyltransferases of different origin. The common hallmark of these exoenzymes is the selective N-ADP-ribosylation of the low molecular mass GTPbinding proteins RhoA, B, and C and inhibition of signal pathways controlled by Rho GTPases. Therefore, C3-like exoenzymes were applied as pharmacological tools for analyses of cellular functions of Rho protein in numerous studies. Recent structural and functional analyses of C3-like exoenzymes provide detailed information on the molecular mechanisms and functional consequences of ADP-ribosylation catalyzed by these toxins. More recently additional non-enzymatic actions of C3-like ADP-ribosyltransferases have been identified showing that C3 transferases from Clostridium botulinum and Clostridium limosum form a GDI-like complex with the Ras-like low molecular mass GTPase Ral without ADP-ribosylation. These results add novel information on the molecular mode of action(s) of C3-like exoenzymes and are discussed in this review.

show abstract

“…In eukaryotic cells, CNF1 binds to its receptor, reported to be the receptor of laminin , and it is endocytosed and released into the cytoplasm by an acidic-dependent mechanism (Contamin et al, 2000). Once in the cytoplasm, CNF1 exerts its enzymatic activity that is represented by deamidation of a pivotal glutamine residue of the guanosine triphosphate (GTP)-binding proteins Rho, Rac, and Cdc42 (glutamine 63 of Rho or glutamine 61 of Rac and Cdc42), giving rise to a glutamic acid (Flatau et al, 1997;Schmidt et al, 1997;Lerm et al, 1999). The glutamine residue modified by CNF1 lies in the switch 2 domain of Rho proteins, which is involved in GTP hydrolysis; thus, the modification exerted by CNF1 blocks the Rho GTPases in their GTP-bound activated state.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic Necrotizing Factor 1 Prevents Apoptosis via the Akt/IκB Kinase Pathway: Role of Nuclear Factor-κB and Bcl-2

Miraglia

Travaglione²,

Meschini

et al. 2007

MBoC

View full text Add to dashboard Cite

Cytotoxic necrotizing factor 1 (CNF1) is a protein toxin produced by some pathogenic strains of Escherichia coli that specifically activates Rho, Rac, and Cdc42 GTPases. We previously reported that this toxin prevents the ultraviolet-Binduced apoptosis in epithelial cells, with a mechanism that remained to be defined. In this work, we show that the proteasomal degradation of the Rho GTPase is necessary to achieve cell death protection, because inhibition of Rho degradation abolishes the prosurvival activity of CNF1. We hypothesize that Rho inactivation allows the activity of Rac to become dominant. This in turn leads to stimulation of the phosphoinositide 3-kinase/Akt/I B kinase/nuclear factor-B prosurvival pathway and to a remarkable modification in the architecture of the mitochondrial network, mainly consisting in the appearance of elongated and interconnected mitochondria. Importantly, we found that Bcl-2 silencing reduces the ability of CNF1 to protect cells against apoptosis and that it also prevents the CNF1-induced mitochondrial changes. It is worth noting that the ability of a bacterial toxin to induce such a remodeling of the mitochondrial network is herein reported for the first time. The possible pathophysiological relevance of this finding is discussed. INTRODUCTIONToday, it is largely acknowledged that apoptosis, besides being an evolutionary conserved form of cell death that plays a pivotal role during development, morphogenesis, and cell homeostasis, is also critically implied in a constantly growing number of diseases (Fadeel and Orrenius, 2005). In fact, apoptosis can be regarded as a widespread strategy exploited by pathogenic bacteria to favor their own survival or spreading in the host , often by producing protein toxins that mediate their long-range cross-talk with host cells. In this context, we have previously reported the ability of a protein toxin from Escherichia coli, namely the cytotoxic necrotizing factor 1 (CNF1), to prevent the ultraviolet-B (UVB)-induced apoptosis and to increase the expression of antiapoptotic Bcl-2 family proteins (Fiorentini et al., 1998). The precise mechanism by which CNF1 allows cells to survive, however, is not yet defined.CNF1 is a protein toxin produced by some pathogenic strains of E. coli mainly involved in extraintestinal infections (Landraud et al., 2000). In eukaryotic cells, CNF1 binds to its receptor, reported to be the receptor of laminin , and it is endocytosed and released into the cytoplasm by an acidic-dependent mechanism (Contamin et al., 2000). Once in the cytoplasm, CNF1 exerts its enzymatic activity that is represented by deamidation of a pivotal glutamine residue of the guanosine triphosphate (GTP)-binding proteins Rho, Rac, and Cdc42 (glutamine 63 of Rho or glutamine 61 of Rac and Cdc42), giving rise to a glutamic acid (Flatau et al., 1997;Schmidt et al., 1997;Lerm et al., 1999). The glutamine residue modified by CNF1 lies in the switch 2 domain of Rho proteins, which is involved in GTP hydrolysis; thus, the modification exerted by CNF1...

show abstract

Gln 63 of Rho is deamidated by Escherichia coli cytotoxic necrotizing factor-1

Cited by 508 publications

References 22 publications

Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction

Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction

C3 exoenzymes, novel insights into structure and action of Rho-ADP-ribosylating toxins

Cytotoxic Necrotizing Factor 1 Prevents Apoptosis via the Akt/IκB Kinase Pathway: Role of Nuclear Factor-κB and Bcl-2

Contact Info

Product

Resources

About