Recent insights into Pasteurella multocida toxin and other G-protein-modulating bacterial toxins.

Over the past few decades, our understanding of the bacterial protein toxins that modulate G proteins has advanced tremendously through extensive biochemical and structural analyses. This article provides an updated survey of the various toxins that target G proteins, ending with a focus on recent mechanistic insights in our understanding of the deamidating toxin family. The dermonecrotic toxin from Pasteurella multocida (PMT) was recently added to the list of toxins that disrupt G-protein signal transduction through selective deamidation of their targets. The C3 deamidase domain of PMT has no sequence similarity to the deamidase domains of the dermonecrotic toxins from Escherichia coli (cytotoxic necrotizing factor [CNF]1-3), Yersinia (CNFY) and Bordetella (dermonecrotic toxin). The structure of PMT-C3 belongs to a family of transglutaminase-like proteins, with active site Cys-His-Asp catalytic triads distinct from E. coli CNF1.

[1]  A. Ganesan,et al.  Pseudomonas aeruginosa Exoenzyme S Disrupts Ras-mediated Signal Transduction by Inhibiting Guanine Nucleotide Exchange Factor-catalyzed Nucleotide Exchange* , 1999, The Journal of Biological Chemistry.

[2]  G. S. Chhatwal,et al.  A Novel C3-like ADP-ribosyltransferase fromStaphylococcus aureus Modifying RhoE and Rnd3* , 2001, The Journal of Biological Chemistry.

[3]  D. Cussac,et al.  Ras, Rap, and Rac Small GTP-binding Proteins Are Targets for Clostridium sordellii Lethal Toxin Glucosylation (*) , 1996, The Journal of Biological Chemistry.

[4]  M. P. Jackson Structure-function analyses of Shiga toxin and the Shiga-like toxins. , 1990, Microbial pathogenesis.

[5]  Yan Zhou,et al.  Structural mechanism of host Rab1 activation by the bifunctional Legionella type IV effector SidM/DrrA , 2010, Proceedings of the National Academy of Sciences.

[6]  R. Goody,et al.  Formation of a Transition-State Analog of the Ras GTPase Reaction by Ras·GDP, Tetrafluoroaluminate, and GTPase-Activating Proteins , 1996, Science.

[7]  J. Bliska,et al.  A secreted protein tyrosine phosphatase with modular effector domains in the bacterial pathogen Salmonella typhimurlum , 1996, Molecular microbiology.

[8]  H. Hamm,et al.  Structural and functional relationships of heterotrimeric G‐proteins , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[9]  L. Pedersen,et al.  Structural evidence that the activation peptide is not released upon thrombin cleavage of factor XIII. , 1995, Thrombosis research.

[10]  K. Yokoyama,et al.  Properties and applications of microbial transglutaminase , 2004, Applied Microbiology and Biotechnology.

[11]  P. Gierschik ADP-ribosylation of signal-transducing guanine nucleotide-binding proteins by pertussis toxin. , 1992, Current topics in microbiology and immunology.

[12]  G. Cornelis,et al.  Molecular and cell biology aspects of plague. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Y. Horiguchi,et al.  Escherichia coli cytotoxic necrotizing factors and Bordetella dermonecrotic toxin: the dermonecrosis-inducing toxins activating Rho small GTPases. , 2001, Toxicon : official journal of the International Society on Toxinology.

[14]  L. Landraud,et al.  Rho GTPase-activating bacterial toxins: from bacterial virulence regulation to eukaryotic cell biology. , 2007, FEMS microbiology reviews.

[15]  M. Mann,et al.  Gln 63 of Rho is deamidated by Escherichia coli cytotoxic necrotizing factor-1 , 1997, Nature.

[16]  J. Vandekerckhove,et al.  Purification and characterization of an ADP-ribosyltransferase produced by Clostridium limosum. , 1992, The Journal of biological chemistry.

[17]  K. Aktories,et al.  His1205 and His1223 are essential for the activity of the mitogenic Pasteurella multocida toxin. , 2003, Biochemistry.

[18]  J. Vandekerckhove,et al.  Rho-ADP-ribosylating exoenzyme from Bacillus cereus. Purification, characterization, and identification of the NAD-binding site. , 1995, Biochemistry.

[19]  G. Milligan,et al.  Action of Pasteurella multocida toxin on Galpha(q) is persistent and independent of interaction with G-protein-coupled receptors. , 2007, Cellular signalling.

[20]  P. Mullan,et al.  Pasteurella multocida Toxin Stimulates Bone Resorption by Osteoclasts via Interaction with Osteoblasts , 1998, Calcified Tissue International.

[21]  A. Lax Bacterial toxins and cancer — a case to answer? , 2005, Nature Reviews Microbiology.

[22]  M. Aepfelbacher,et al.  Disturbance of endothelial barrier function by bacterial toxins and atherogenic mediators: a role for Rho/Rho kinase , 2001, Cellular microbiology.

[23]  A. Hall,et al.  The rho gene product expressed in E. coli is a substrate of botulinum ADP-ribosyltransferase C3. , 1989, Biochemical and biophysical research communications.

[24]  Sheng Zhang,et al.  A Receptor-Modifying Deamidase in Complex with a Signaling Phosphatase Reveals Reciprocal Regulation , 2006, Cell.

[25]  Masami Miyake,et al.  Crystal structures reveal a thiol protease-like catalytic triad in the C-terminal region of Pasteurella multocida toxin , 2007, Proceedings of the National Academy of Sciences.

[26]  K. Orth,et al.  A newly discovered post-translational modification--the acetylation of serine and threonine residues. , 2007, Trends in biochemical sciences.

[27]  R. Verma,et al.  Humanized immunotoxins: A new generation of immunotoxins for targeted cancer therapy , 2009, Cancer science.

[28]  C. Fiorentini,et al.  Bacterial protein toxins: current and potential clinical use. , 2008, Current medicinal chemistry.

[29]  K. Aktories,et al.  Action of Pasteurella multocida Toxin Depends on the Helical Domain of Gαq* , 2004, Journal of Biological Chemistry.

[30]  B. Deurs,et al.  Delivery into cells: lessons learned from plant and bacterial toxins , 2005, Gene Therapy.

[31]  R. Kahn,et al.  The Structure of RalF, an ADP-ribosylation Factor Guanine Nucleotide Exchange Factor from Legionella pneumophila, Reveals the Presence of a Cap over the Active Site* , 2005, Journal of Biological Chemistry.

[32]  K. Christopher Garcia,et al.  Mechanistic and structural insights into the proteolytic activation of Vibrio cholera MARTX toxin , 2009, Nature chemical biology.

[33]  S. Lea,et al.  EspM2 is a RhoA guanine nucleotide exchange factor , 2010, Cellular microbiology.

[34]  E. Rozengurt,et al.  Pasteurella multocida toxin, a potent mitogen, stimulates protein kinase C-dependent and -independent protein phosphorylation in Swiss 3T3 cells. , 1990, The Journal of biological chemistry.

[35]  T. Ohnishi,et al.  Pasteurella multocida toxin and Bordetella bronchiseptica dermonecrotizing toxin elicit similar effects on cultured cells by different mechanisms. , 1998, The Journal of veterinary medical science.

[36]  K. Matsumoto,et al.  Epidermal cell differentiation inhibitor ADP-ribosylates small GTP-binding proteins and induces hyperplasia of epidermis. , 1992, The Journal of biological chemistry.

[37]  B. Raymond,et al.  Bacterial Guanine Nucleotide Exchange Factors SopE-Like and WxxxE Effectors , 2010, Infection and Immunity.

[38]  J. Nilsson,et al.  Crystal Structure of ADP-ribosylated Ribosomal Translocase from Saccharomyces cerevisiae* , 2004, Journal of Biological Chemistry.

[39]  L. Landraud,et al.  Deamidation of RhoA glutamine 63 by the Escherichia coli CNF1 toxin requires a short sequence of the GTPase switch 2 domain. , 2000, Biochemical and biophysical research communications.

[40]  M. Aepfelbacher,et al.  Pasteurella multocida toxin increases endothelial permeability via Rho kinase and myosin light chain phosphatase. , 1998, Journal of immunology.

[41]  T. Katada,et al.  Two guanine nucleotide-binding proteins in rat brain serving as the specific substrate of islet-activating protein, pertussis toxin. Interaction of the alpha-subunits with beta gamma-subunits in development of their biological activities. , 1986, The Journal of biological chemistry.

[42]  Karla J. F. Satchell,et al.  Characterization of the Enzymatic Activity of the Actin Cross-linking Domain from the Vibrio cholerae MARTXVc Toxin* , 2008, Journal of Biological Chemistry.

[43]  C. Fiorentini,et al.  Toxin-induced activation of the G protein p21 Rho by deamidation of glutamine , 1997, Nature.

[44]  Qing Deng,et al.  Molecular mechanisms of the cytotoxicity of ADP-ribosylating toxins. , 2008, Annual review of microbiology.

[45]  P. Casey,et al.  G protein involvement in receptor-effector coupling. , 1988, The Journal of biological chemistry.

[46]  Kerri‐Lynn Sheahan,et al.  Inactivation of small Rho GTPases by the multifunctional RTX toxin from Vibrio cholerae , 2007, Cellular microbiology.

[47]  A. Gilman,et al.  Expression of Gs alpha in Escherichia coli. Purification and properties of two forms of the protein. , 1989, The Journal of biological chemistry.

[48]  C. Hoffmann,et al.  CNF and DNT. , 2004, Reviews of physiology, biochemistry and pharmacology.

[49]  B. Wilson,et al.  Pasteurella multocida Toxin Stimulates Mitogen-activated Protein Kinase via Gq/11-dependent Transactivation of the Epidermal Growth Factor Receptor* , 2000, The Journal of Biological Chemistry.

[50]  Samuel I. Miller,et al.  Structure and function of Salmonella SifA indicate that its interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation. , 2008, Cell host & microbe.

[51]  K. Aktories,et al.  Biological Activity of a C-Terminal Fragment ofPasteurella multocida Toxin , 2001, Infection and Immunity.

[52]  L. Stryer,et al.  G proteins: a family of signal transducers. , 1986, Annual review of cell biology.

[53]  B. Wilson,et al.  Calcineurin‐independent inhibition of 3T3‐L1 adipogenesis by Pasteurella multocida toxin: suppression of Notch1, stabilization of β‐catenin and pre‐adipocyte factor 1 , 2007, Cellular microbiology.

[54]  K. Aktories,et al.  Glucosylation and ADP ribosylation of rho proteins: effects on nucleotide binding, GTPase activity, and effector coupling. , 1998, Biochemistry.

[55]  A. Parmeggiani,et al.  Properties and regulation of the GTPase activities of elongation factors Tu and G, and of initiation factor 2 , 1981, Molecular and Cellular Biochemistry.

[56]  L. Van Aelst,et al.  Rho GTPases and signaling networks. , 1997, Genes & development.

[57]  W. Kabsch,et al.  The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. , 1997, Science.

[58]  J. Ballard,et al.  Clostridium difficile Toxins: Mechanism of Action and Role in Disease , 2005, Clinical Microbiology Reviews.

[59]  T. Katada,et al.  Bacterial toxins as probe for receptor-Gi coupling. , 1990, Advances in second messenger and phosphoprotein research.

[60]  David E. Clapham,et al.  Roles of G protein subunits in transmembrane signalling , 1988, Nature.

[61]  J. Tropea,et al.  Crystal structure of the Yersinia pestis GTPase activator YopE , 2002, Protein science : a publication of the Protein Society.

[62]  D. Lambright,et al.  Legionella pneumophila proteins that regulate Rab1 membrane cycling , 2007, Nature.

[63]  T. Hughes,et al.  Identification of a Bacterial Type III Effector Family with G Protein Mimicry Functions , 2006, Cell.

[64]  K. Aktories,et al.  Identification of the Region of Rho Involved in Substrate Recognition by Escherichia coli Cytotoxic Necrotizing Factor 1 (CNF1)* , 1999, The Journal of Biological Chemistry.

[65]  I. Lebrun,et al.  Bacterial toxins: an overview on bacterial proteases and their action as virulence factors. , 2009, Mini reviews in medicinal chemistry.

[66]  Lysine and Polyamines Are Substrates for Transglutamination of Rho by the BordetellaDermonecrotic Toxin , 2001, Infection and Immunity.

[67]  E. Suzuki,et al.  Crystal Structure of Red Sea Bream Transglutaminase* , 2001, The Journal of Biological Chemistry.

[68]  P. Boquet,et al.  Molecular localization of the Escherichia coli cytotoxic necrotizing factor CNF1 cell‐binding and catalytic domains , 1997, Molecular microbiology.

[69]  S. Rhee,et al.  Regulation of inositol phospholipid-specific phospholipase C isozymes. , 1992, The Journal of biological chemistry.

[70]  B. Wilson,et al.  Application of intact cell-based NFAT-beta-lactamase reporter assay for Pasteurella multocida toxin-mediated activation of calcium signaling pathway. , 2008, Toxicon : official journal of the International Society on Toxinology.

[71]  B. Trask,et al.  Evolution of the mammalian G protein α subunit multigene family , 1992, Nature Genetics.

[72]  R. Collier,et al.  Diphtheria toxin and Pseudomonas aeruginosa exotoxin A: active-site structure and enzymic mechanism. , 1992, Current Topics in Microbiology and Immunology.

[73]  D. Ejima,et al.  Crystal Structure of Microbial Transglutaminase fromStreptoverticillium mobaraense * , 2002, The Journal of Biological Chemistry.

[74]  K. Aktories,et al.  The N-terminal Domain of Pseudomonas aeruginosaExoenzyme S Is a GTPase-activating Protein for Rho GTPases* , 1999, The Journal of Biological Chemistry.

[75]  K. Aktories,et al.  Rho GTPases as Targets of Bacterial Protein Toxins , 2000, Biological chemistry.

[76]  D. Hinode,et al.  Purification and Characterization of Arginine Carboxypeptidase Produced by Porphyromonas gingivalis , 2002, Infection and Immunity.

[77]  A. C. Murphy,et al.  Pasteurella multocida toxin, a potent mitogen, increases inositol 1,4,5-trisphosphate and mobilizes Ca2+ in Swiss 3T3 cells. , 1991, The Journal of biological chemistry.

[78]  J. Bliska,et al.  The RhoGAP activity of the Yersinia pseudotuberculosis cytotoxin YopE is required for antiphagocytic function and virulence , 2000, Molecular microbiology.

[79]  M. Weidmann,et al.  Toxins A and B from Clostridium difficile differ with respect to enzymatic potencies, cellular substrate specificities, and surface binding to cultured cells. , 1997, The Journal of clinical investigation.

[80]  B. Wilson,et al.  Physical and Functional Interactions of Gαq with Rho and Its Exchange Factors* , 2001, The Journal of Biological Chemistry.

[81]  L. Birnbaumer,et al.  Studies on nucleotide and receptor regulation of Gi proteins: effects of pertussis toxin. , 1989, Molecular endocrinology.

[82]  M. Rodnina,et al.  Codon‐dependent conformational change of elongation factor Tu preceding GTP hydrolysis on the ribosome. , 1995, The EMBO journal.

[83]  A. C. Murphy,et al.  Pasteurella multocida toxin selectively facilitates phosphatidylinositol 4,5-bisphosphate hydrolysis by bombesin, vasopressin, and endothelin. Requirement for a functional G protein. , 1992, The Journal of biological chemistry.

[84]  T. Yeates,et al.  Connecting actin monomers by iso-peptide bond is a toxicity mechanism of the Vibrio cholerae MARTX toxin , 2008, Proceedings of the National Academy of Sciences.

[85]  K. Aktories,et al.  Modulation of Host Cell Gene Expression through Activation of STAT Transcription Factors by Pasteurella multocida Toxin* , 2007, Journal of Biological Chemistry.

[86]  B. Wilson,et al.  Pasteurella multocida toxin as a tool for studying Gq signal transduction. , 2004, Reviews of physiology, biochemistry and pharmacology.

[87]  S R Sprang,et al.  G protein mechanisms: insights from structural analysis. , 1997, Annual review of biochemistry.

[88]  E. Rozengurt,et al.  Pasteurella multocida Toxin, a Potent Intracellularly Acting Mitogen, Induces p125@ and Paxillin Tyrosine Phosphorylation, Actin Stress Fiber Formation, and Focal Contact Assembly in Swiss 3T3 Cells (*) , 1996, The Journal of Biological Chemistry.

[89]  B. Nürnberg,et al.  Pasteurella multocida toxin activates Gbetagamma dimers of heterotrimeric G proteins. , 2009, Cellular signalling.

[90]  S. Sprang,et al.  Structure of RGS4 Bound to AlF4 −-Activated Giα1: Stabilization of the Transition State for GTP Hydrolysis , 1997, Cell.

[91]  A. Hall,et al.  Rho GTPases and the actin cytoskeleton. , 1998, Science.

[92]  E. Rozengurt,et al.  Escherichia coli Cytotoxic Necrotizing Factor andPasteurella multocida Toxin Induce Focal Adhesion Kinase Autophosphorylation and Src Association , 2001, Infection and Immunity.

[93]  R. Wyatt,et al.  Several GTP-binding proteins, including p21c-H-ras, are preferred substrates of Pseudomonas aeruginosa exoenzyme S. , 1989, The Journal of biological chemistry.

[94]  G. Johnson,et al.  Gα12 and Gα13 Stimulate Rho-dependent Stress Fiber Formation and Focal Adhesion Assembly (*) , 1995, The Journal of Biological Chemistry.

[95]  R. Sowdhamini,et al.  Localization of Functional Domains of the Mitogenic Toxin of Pasteurella multocida , 2001, Infection and Immunity.

[96]  A. Wittinghofer,et al.  Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE , 2002, The EMBO journal.

[97]  G. Frankel,et al.  EspT triggers formation of lamellipodia and membrane ruffles through activation of Rac-1 and Cdc42 , 2008, Cellular microbiology.

[98]  P. Casey,et al.  Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins. , 1997, The Biochemical journal.

[99]  B. Wilson,et al.  Pasteurella multocida Toxin Activates the Inositol Triphosphate Signaling Pathway in Xenopus Oocytes via Gqα-coupled Phospholipase C-β1* , 1997, The Journal of Biological Chemistry.

[100]  A. Wittinghofer,et al.  Structure of the ExoS GTPase activating domain , 2001, FEBS letters.

[101]  U. Engel,et al.  LARG and mDia1 Link Gα12/13 to Cell Polarity and Microtubule Dynamics , 2008 .

[102]  Shihori Tanabe,et al.  Regulation of RGS-RhoGEFs by Gα12 and Gα13 Proteins , 2004 .

[103]  A. R. Merrill,et al.  The life and death of translation elongation factor 2. , 2006, Biochemical Society transactions.

[104]  T. Frisan,et al.  Cytolethal distending toxins. , 2004, Reviews of physiology, biochemistry and pharmacology.

[105]  B. Wilson,et al.  Activation of Gαi and Subsequent Uncoupling of Receptor-Gαi Signaling by Pasteurella multocida Toxin* , 2008, Journal of Biological Chemistry.

[106]  D. Jeenes,et al.  Protein-glutaminase from Chryseobacterium proteolyticum, an enzyme that deamidates glutaminyl residues in proteins. Purification, characterization and gene cloning. , 2001, European journal of biochemistry.

[107]  Mohammad Reza Ahmadian,et al.  Confirmation of the arginine-finger hypothesis for the GAP-stimulated GTP-hydrolysis reaction of Ras , 1997, Nature Structural Biology.

[108]  N. Grishin,et al.  BTLCP proteins: a novel family of bacterial transglutaminase-like cysteine proteinases. , 2004, Trends in biochemical sciences.

[109]  Shenghao Jin,et al.  Activation of RhoA by Association of Gα13 with Dbl , 2000 .

[110]  J. Galán,et al.  A Salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion , 1999, Nature.

[111]  K. Aktories,et al.  The Yersinia pseudotuberculosis Cytotoxic Necrotizing Factor (CNFY) Selectively Activates RhoA* , 2004, Journal of Biological Chemistry.

[112]  M. Pallen,et al.  Subversion of actin dynamics by EspM effectors of attaching and effacing bacterial pathogens , 2008, Cellular microbiology.

[113]  M. Rodnina,et al.  Hydrolysis of GTP by elongation factor G drives tRNA movement on the ribosome , 1997, Nature.

[114]  M. Noble,et al.  Structure of arylamine N-acetyltransferase reveals a catalytic triad , 2000, Nature Structural Biology.

[115]  Karla J. F. Satchell MARTX, Multifunctional Autoprocessing Repeats-in-Toxin Toxins , 2007, Infection and Immunity.

[116]  K. Aktories,et al.  Structure and mode of action of clostridial glucosylating toxins: the ABCD model. , 2008, Trends in microbiology.

[117]  S R Sprang,et al.  G proteins, effectors and GAPs: structure and mechanism. , 1997, Current opinion in structural biology.

[118]  H. Ohta,et al.  Cytotoxic Necrotizing Factor Type 2 Produced by Pathogenic Escherichia coli Deamidates a Gln Residue in the Conserved G-3 Domain of the Rho Family and Preferentially Inhibits the GTPase Activity of RhoA and Rac1 , 1999, Infection and Immunity.

[119]  P. Boquet,et al.  Structure of the Rho-activating domain of Escherichia coli cytotoxic necrotizing factor 1 , 2001, Nature Structural Biology.

[120]  B. Wilson,et al.  The C3 domain of Pasteurella multocida toxin is the minimal domain responsible for activation of Gq‐dependent calcium and mitogenic signaling , 2008, Protein science : a publication of the Protein Society.

[121]  G. Schultz,et al.  Pleiotropic Effects of Pasteurella multocida Toxin Are Mediated by Gq-dependent and -independent Mechanisms , 2001, The Journal of Biological Chemistry.

[122]  J. Chai,et al.  Structural insights into host GTPase isoform selection by a family of bacterial GEF mimics , 2009, Nature Structural &Molecular Biology.

[123]  E. Lemichez,et al.  Bacterial toxins activating Rho GTPases. , 2005, Current topics in microbiology and immunology.

[124]  Karla J. F. Satchell,et al.  Genetic determination of essential residues of the Vibrio cholerae actin cross‐linking domain reveals functional similarity with glutamine synthetases , 2009, Molecular microbiology.

[125]  P. Sternweis,et al.  Regulation of phospholipase C by G proteins. , 1992, Trends in biochemical sciences.

[126]  Hans Wolf-Watz,et al.  Identification of a molecular target for the Yersinia protein kinase A. , 2007, Molecular cell.

[127]  Y. Horiguchi,et al.  Characterization of the Membrane-targeting C1 Domain in Pasteurella multocida Toxin* , 2010, The Journal of Biological Chemistry.

[128]  Bruce R. Conklin,et al.  Structural elements of Gα subunits that interact with Gβγ, receptors, and effectors , 1993, Cell.

[129]  E. Rozengurt,et al.  Pasteurella multocida toxin: potent mitogen for cultured fibroblasts. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[130]  J. Barbieri,et al.  Pseudomonas aeruginosa ExoT ADP-ribosylates CT10 Regulator of Kinase (Crk) Proteins* , 2003, Journal of Biological Chemistry.

[131]  F. Gisou van der Goot,et al.  The bacterial toxin toolkit , 2001, Nature Reviews Molecular Cell Biology.

[132]  K. Aktories,et al.  The Rho-deamidating cytotoxic necrotizing factor 1 from Escherichia coli possesses transglutaminase activity. Cysteine 866 and histidine 881 are essential for enzyme activity. , 1998, The Journal of biological chemistry.

[133]  B. Wilson,et al.  Pasteurella multocida toxin activation of heterotrimeric G proteins by deamidation , 2009, Proceedings of the National Academy of Sciences.

[134]  D. Ladant,et al.  Bordetella pertussis adenylate cyclase toxin: a versatile screening tool. , 2002, Toxicon : official journal of the International Society on Toxinology.

[135]  B. Wilson,et al.  Differential Modulation and Subsequent Blockade of Mitogenic Signaling and Cell Cycle Progression by Pasteurella multocida Toxin , 2000, Infection and Immunity.

[136]  A. Joachimiak,et al.  Crystal structure of hypothetical protein YfiH from Shigella flexneri at 2 Å resolution , 2006, Proteins.

[137]  Y. Horiguchi,et al.  In Vivo Modifications of Small GTPase Rac and Cdc42 by Bordetella Dermonecrotic Toxin , 2002, Infection and Immunity.

[138]  R. Isberg,et al.  A Bifunctional Bacterial Protein Links GDI Displacement to Rab1 Activation , 2007, Science.

[139]  J. Bodley,et al.  Occurrence of diphthamide in archaebacteria , 1983, Journal of bacteriology.

[140]  Y. Shimonishi,et al.  Activation of Rho through a cross‐link with polyamines catalyzed by Bordetella dermonecrotizing toxin , 2000, The EMBO journal.

[141]  T. Kashimoto,et al.  Identification of Functional Domains ofBordetella Dermonecrotizing Toxin , 1999, Infection and Immunity.

[142]  J. Dixon,et al.  A Yersinia Effector and a Pseudomonas Avirulence Protein Define a Family of Cysteine Proteases Functioning in Bacterial Pathogenesis , 2002, Cell.

[143]  M. Strathmann,et al.  G protein diversity: a distinct class of alpha subunits is present in vertebrates and invertebrates. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[144]  J. Sun,et al.  Pseudomonas aeruginosa ExoS and ExoT. , 2004, Reviews of physiology, biochemistry and pharmacology.

[145]  C. Sasakawa,et al.  IpgB1 Is a Novel Shigella Effector Protein Involved in Bacterial Invasion of Host Cells , 2005, Journal of Biological Chemistry.

[146]  K. Aktories,et al.  Pasteurella multocida Toxin-induced Activation of RhoA Is Mediated via Two Families of Gα Proteins, Gαq and Gα12/13* , 2005, Journal of Biological Chemistry.

[147]  J. Coburn,et al.  Exoenzyme S of Pseudomonas aeruginosa ADP-ribosylates the intermediate filament protein vimentin , 1989, Infection and immunity.

[148]  B. Wilson,et al.  Dual Actions of the G&agr;q Agonist Pasteurella multocida Toxin to Promote Cardiomyocyte Hypertrophy and Enhance Apoptosis Susceptibility , 2002, Circulation research.

[149]  K. Aktories,et al.  Microbial toxins and the glycosylation of rho family GTPases. , 2000, Current opinion in structural biology.

[150]  S. Smerdon,et al.  Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP , 1997, Nature.

[151]  A. Ganesan,et al.  Pseudomonas aeruginosa Exoenzyme S ADP-ribosylates Ras at Multiple Sites* , 1998, The Journal of Biological Chemistry.

[152]  C. E. Stebbins,et al.  Yersinia Virulence Depends on Mimicry of Host Rho-Family Nucleotide Dissociation Inhibitors , 2006, Cell.

[153]  K. Aktories,et al.  Exchange of a Single Amino Acid Switches the Substrate Properties of RhoA and RhoD toward Glucosylating and Transglutaminating Toxins* , 2006, Journal of Biological Chemistry.

[154]  K. Procházková,et al.  Structure-Function Analysis of Inositol Hexakisphosphate-induced Autoprocessing of the Vibrio cholerae Multifunctional Autoprocessing RTX Toxin* , 2008, Journal of Biological Chemistry.

[155]  Katrin Rittinger,et al.  Structure at 1.65 Å of RhoA and its GTPase-activating protein in complex with a transition-state analogue , 1997, Nature.

[156]  J. Segura-Aguilar,et al.  Botulinum neurotoxin: Evolution from poison, to research tool - onto medicinal therapeutic and future pharmaceutical panacea , 2007, Neurotoxicity Research.

[157]  T. Pape,et al.  Elongation factor Tu, a GTPase triggered by codon recognition on the ribosome: mechanism and GTP consumption. , 1995, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[158]  R. Kahn,et al.  ADP-ribosylation of Gs promotes the dissociation of its alpha and beta subunits. , 1984, The Journal of biological chemistry.

[159]  L. Nilsson,et al.  Kinetic determination of the effects of ADP-ribosylation on the interaction of eukaryotic elongation factor 2 with ribosomes. , 1990, The Journal of biological chemistry.

[160]  G. Minasov,et al.  Structural and Molecular Mechanism for Autoprocessing of MARTX Toxin of Vibrio cholerae at Multiple Sites* , 2009, The Journal of Biological Chemistry.

[161]  Y. Yamaguchi,et al.  N-terminal Short Sequences of α Subunits of the G12Family Determine Selective Coupling to Receptors* , 2003, The Journal of Biological Chemistry.

[162]  K. Aktories,et al.  Identification of the C-terminal Part of BordetellaDermonecrotic Toxin as a Transglutaminase for Rho GTPases* , 1999, The Journal of Biological Chemistry.