Pseudomonas Translocation

In eukaryotic cells, elongation factor-2 (eEF-2) used in translocation is inactivated through ADP-ribosylation by Pseudomonas and Diphtheria toxins. 

C. botulinum toxins belong to the AB group of toxins, which also includes diphtheria toxin, pseudomonas exotoxin A, anthrax toxin, Shiga(like) toxin, cholera toxin, pertussis toxin, and plant toxins, e.g., ricin. Moiety A has an enzymatic activity and usually modified cellular-target entering cytosol. Moiety B consists of one or more components and binds the toxin to surface receptors, and is responsible for translocation of the A component into cells. AB toxins are produced in a non-active form and are activated by a split between two cysteine residues within a region (Falnes and Sandvig, 2000). 

ATP out of and ADP into the mitochondrion. Translocation is inhibited by two well-known toxins, atractyloside and bongkrekic acid, the former a glucoside found in the Mediterranean thistle and the latter produced by a Pseudomonas bacterium. 

Unlike diphtheria toxin, little is known about the structures required for the translocation of the enzymatic subunit of PT. In diphtheria toxin and Pseudomonas aeruginosa exotoxin A, the B moiety can be clearly subdivided into two distinct domains, one responsible for receptor binding, composed essentially of (3 sheets, and one responsible for translocation of the A subunits, essentially composed of a helices (Allured etal., 1986 Choe etal., 1992). There is no clear translocation domain in PT, and much less is known about the internalization step of PT, compared to diphtheria toxin and exotoxin A. 

Like diphtheria toxin. Pseudomonas aeruginosa exotoxin A requires low pH to act (FitzGerald ef al., 1980). In spite of this, it has not been possible to induce translocation of Pseudomonas toxin across the surface membrane by exposure to low pH. It appears that the toxin must be transported beyond the endosomes, possibly to the trans-Golgi network or even to the endoplasmic reticulum to find conditions required for translocation (Chaudhary et al., 1990). In fact domain III ends with an amino acid sequence that (after removal of a terminal... 

Fusion proteins have been constructed from peptide epitopes from influenza A antigens and the binding and translocation domains of Pseudomonas exotoxin A (Donelly ef al., 1993). When target cells were incubated with these fusion proteins, and subsequently exposed to cytotoxic T lymphocytes (CTLs) specific for the relevant epitopes, a CTL mediate lysis of the target cells was observed. These experiments suggest that the translocation machinery supplied by protein toxins may be useful tools for bringing peptides into cells for presentation via the major histocompatibility class I (MHC I) system. It should be noted that no direct evidence was provided that the translocation occurred by the toxin pathway, and it cannot be excluded that the toxin was only instrumental in accumulating the peptide on the surface of the cells and in the endocytic pathway. 

Ogata M, Chaudhary VK, Pastan I, FitzGerald DJ (1990) Processing of Pseudomonas exotoxin by a cellular protease results in the generation of a 37,000-Da toxin fragment that is translocated to the cytosol. J Biol Chem 265 20678-20685. 

Prior Tl, FitzGerald DJ, Pastan I (1992) Translocation mediated by domain II of Pseudomonas exotoxin A Transport of barnase into the cytosol. Biochemistry 31 3555-3559. 

Wehrfritz J-M, Carter JP, Soiro S, Richardson DJ (1997) Hydroxylamine oxidation in heterotro-phic nitrate-reducing soil bacteria and purification of hydroxylamine cytochrome c oxidore-ductase from Pseudomonas species. Arch Microbiol 166 421 —424 Wehrfritz J-M, Reilly A, Spiro S, Richardson DJ (1993) Purification of hydroxylamine oxidase from Thiosphaera pantotropha. Identification of electron acceptors that couple heterotrophic nitrification to aerobic denitrification. FEBS Lett 335 246-250 Wetzstein H-G, Ferguson SJ (1985) Respiration-dependent proton translocation and the mechanism of proton motive force generation in Nitrobacter winogradskyi. FEMS Microbiol Lett 30 87-92... 

Leamon CP, Pastan I, Low PS. Cytotoxicity of folate-pseudomonas exotoxin conjugates toward tumor cells contribution of translocation domain. J Biol Chem 1993 268 24847-24854. 

Zhang L, Zhao J, Wang T et al. (2008) HER2-targeting recombinant protein with truncated pseudomonas exotoxin A translocation domain efficiently kills breast cancer cells. Cancer Biol Ther 7 1226 1231... 

Bongkrekic acid 3-carboxymethyl-17-methoxy-6,18,21-trimethyldocosa-2,4,8,12,14,18,20-heptaene-dioic acid, M, 486.61. B.a. is one of 2 toxic antibiotics produced by Pseudomonas cocovenenans in spoiled bongkrek (a coconut product consumed in Indonesia). It is an inhibitor of adenine nucleoside translocation, and it affects carbohydrate metabolism. 

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