Evolutionary origin of pathogenic determinants in enterotoxigenic Escherichia coli and Vibrio cholerae O1

Yamamoto, Tatsuo; Gojobori, Takashi; Yokota, Takeshi

doi:10.1128/jb.169.3.1352-1357.1987

Cited by 106 publications

(65 citation statements)

References 61 publications

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“…We have previously reported the structure of the LT AB, holotoxin at 1.95 A resolution [1,2] subunit consists in the holotoxin of a single peptide chain containing 240 residues [3,4]. Its tertiary structure clearly consists of two domains (Fig.…”

Section: Introductionmentioning

confidence: 99%

Structure of partially‐activated E. coli heat‐labile enterotoxin (LT) at 2.6 Å resolution

et al. 1994

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Biological toxicity of E. coli heat-labile enterotoxin and the closely related cholera toxin requires that the assembled toxin be activated by proteolytic cleavage of the A subunit and reduction of a disulfide bond internal to the A subunit. The structural role served by this reduction and cleavage is not known, however. We have crystallographically determined the structure of the E. coli heat-labile enterotoxin AB, hexamer in which the A subunit has been cleaved by trypsin between residues 192 and 195. The toxin is thus partially activated, in that it has been cleaved but the disulfide bond has not been reduced. The structure of the A subunit in the cleaved toxin is substantially the same as that previously observed for the uncleaved AB, structure, suggesting that although such cleavage is required for biological activity of the toxin it does not by itself cause a conformational change.

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Section: Introductionmentioning

confidence: 99%

Structure of partially‐activated E. coli heat‐labile enterotoxin (LT) at 2.6 Å resolution

et al. 1994

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“…4. Comparison of the amino acid sequences of the region adjacent to a glutamic acid residue suggested to be involved in catalysis of the ADP-ribosylation by various transferases (Lim, C. limosum ADP-ribosyltransferase [28]; C3N, C. botulinum C3 transferase [26]; C3P, C. botulinum C3 transferase [25]; EDIN, S. aureus transferase [27]; Cer, B. cereus transferase [23]; CT, cholera toxin [30]; LT, E. coli heat labile toxin [43]; MTX, mosquitocidal toxin from B. sphaericus [44]; PT, pertussis toxin [45]; T2, bacteriophage ADPribosyltransferase T2 [32]; mRT6, mouse homologue of the rat T cell alloantigen RT6 [46]; rMT, rabbit muscle ADP-ribosyltransferase [33]; ETA, Pseudomonas exotoxin A [47]; DT, diphtheria toxin [481.…”

Section: Resultsmentioning

confidence: 99%

Analysis of the catalytic site of the actin ADP‐ribosylating Clostridium perfringens iota toxin

Damme¹,

Jung

Hofmann

et al. 1996

FEBS Letters

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“…Sequence of the immunogenic surface peptide CTP3, which is conserved in the B subunits of CT and LT. Overall, the sequence identity between CT and LT is approximately 80070, for both the A and B subunits (Dallas & Falkow, 1980;Yamamoto et al, 1987). Residues of the peptide seen in the X-ray and NMR structures of the peptide-antibody complex are indicated.…”

Section: Shoham Et Atmentioning

confidence: 99%

Structural diversity in a conserved cholera toxin epitope involved in ganglioside binding

et al. 1995

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Cholera is a widespread disease for which there is no efficient vaccine. A better understanding of the conformational rearrangements at the epitope might be very helpful for the development of a good vaccine. Cholera toxin (CT) as well as the closely related heat-labile toxin from Escherichia coli (LT) are composed of two subunits, A and B, which form an oligomeric assembly AB5. Residues 50-64 on the surface of the B subunits comprise a conserved loop (CTP3), which is involved in saccharide binding to the receptor on epithelial cells. This loop exhibits remarkable conformational plasticity induced by environmental constraints. The crystal structure of this loop is compared in the free and receptor-bound toxins as well as in the crystal and solution structures of a complex with TE33, a monoclonal antibody elicited against CTP3. In the toxins this loop forms an irregular structure connecting a &strand to the central a-helix. Ser 55 and Gln 56 exhibit considerable conformational variability in the five subunits of the unliganded toxins. Saccharide binding induces a change primarily in Ser 55 and Gln 56 to a conformation identical in all five copies. Thus, saccharide binding confers rigidity upon the loop. The conformation of CTP3 in complex with TE33 is quite different. The amino-terminal part of CTP3 forms a 0-turn that fits snugly into a deep binding pocket on TE33, in both the crystal and NMR-derived solution structure. Only 8 and 12 residues out of 15 are seen in the NMR and crystal structures, respectively. Despite these conformational differences, TE33 is cross-reactive with intact CT, albeit with a thousandfold decrease in affinity. This suggests a different interaction of TE33 with intact CT.Keywords: antipeptide antibody; conformational rearrangements at the epitope; cholera toxin; flexible loop involved in receptor binding Cholera toxin (CT) as well as the closely related heat-labile toxin from Escherichia coli (LT) are composed of two types of subunits, A and B, which form an oligomeric assembly AB, (Sixma et al., 1991). The initial step in the toxin-induced process leading to the symptoms of diarrhea is the attachment of the B subunits to intestinal epithelial cells. Immunogenic moieties on the surface of the B, molecule therefore constitute suitable targets for the development of peptide vaccines against cholera. Residues 50-64 of the B subunit form such a surface loop that is entirely conserved between CT and LT ( Fig. 1; Kinemage 1). This loop is directly involved in carbohydrate bind-

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Evolutionary origin of pathogenic determinants in enterotoxigenic Escherichia coli and Vibrio cholerae O1

Cited by 106 publications

References 61 publications

Structure of partially‐activated E. coli heat‐labile enterotoxin (LT) at 2.6 Å resolution

Structure of partially‐activated E. coli heat‐labile enterotoxin (LT) at 2.6 Å resolution

Analysis of the catalytic site of the actin ADP‐ribosylating Clostridium perfringens iota toxin

Structural diversity in a conserved cholera toxin epitope involved in ganglioside binding

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