Tetanus toxin.

Bizzini, B

doi:10.1128/mmbr.43.2.224-240.1979

Cited by 73 publications

(25 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Tetanus is a mammalian disease generated by the infection of a wound by the anaerobic bacillus Clostridium tetani. Clinically, this is manifested by a spastic paralysis induced by prevention of inhibitory neurotransmitter (4-aminobutyric acid and glycine) release in the central nervous system (for reviews see: Wellhoner, 1982Wellhoner, , 1992Niemann, 1991 ;Hatheway, 1990;Simpson, 1986Simpson, , 1989Habermann and Dreyer, 1986;Bizzini, 1979). The blockade of neurotransmitter exocytosis is due to a highly potent neurotoxin, tetanus toxin (TeTx), which is a 150-kDa protein composed of two disulfide-linked polypeptide chains, a light chain L (52 kDa) and a heavy chain H (98 kDa).…”

mentioning

confidence: 99%

Solid‐phase synthesis, conformational analysis and in vitro cleavage of synthetic human synaptobrevin II 1–93 by tetanus toxin L chain

Cornille

Goudreau

Ficheux

et al. 1994

European Journal of Biochemistry

View full text Add to dashboard Cite

A 93-residue peptide corresponding to the cytosolic domain of a human vesicle associated membrane protein (VAMP or synaptobrevin) has been prepared by solid-phase peptide synthesis in order to investigate the proteolytic activity of the tetanus toxin light chain (TeTx L chain). This protein has been recently reported to inactivate the neuronal rat synaptobrevin I1 by proteolysis. We show in this study that the synthetic human synaptobrevin I1 1-93 (Syb I1 1-93) as well as an Nterminus-shortened 69-residue peptide were cleaved selectively at the Gln76-Phe77 peptide bond by TeTx L chain while shorter peptides were not. A Michaelis constant K , = 192 & 2 pM and a catalytic constant k,,, = 0.5 min-I were found for the 93-residue peptide. A neutral optimum pH for the cleavage rate, an inhibition by preincubation of the toxin with well known nonspecific inhibitors of metallopeptidases as well as a zinc-dependent enzyme activity suggest that TeTx belongs to the zinc endopeptidase family. Moreover an activation by reducing agents and an inhibition by cysteine-modifying chemical reagents indicate a critical thiol dependency. Among several specific inhibitors of zinc endopeptidases tested, none could inhibit TeTx L chain even at high concentration. Structural studies by 600-MHz 'H-NMR showed that in water or dimethylsulfoxide the peptide Syb I1 1-93 and shorter fragments did not present well definkd conformations. Nevertheless protein-protein interactions have been shown for the peptides Syb I1 1-93 and 25-93 but not for Syb I1 51-93, a fragment not cleaved by TeTx L chain.Tetanus is a mammalian disease generated by the infection of a wound by the anaerobic bacillus Clostridium tetani. Clinically, this is manifested by a spastic paralysis induced by prevention of inhibitory neurotransmitter (4-aminobutyric acid and glycine) release in the central nervous system (for reviews see:

show abstract

mentioning

confidence: 99%

Solid‐phase synthesis, conformational analysis and in vitro cleavage of synthetic human synaptobrevin II 1–93 by tetanus toxin L chain

Cornille

Goudreau

Ficheux

et al. 1994

European Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

“…The neurotoxin produced by Clostridium tetani belongs to the family of bacterial toxins known to have an intracellular target [1]. Tetanus toxin (TI') consists of two functional subunits: C fragment is involved in the binding and translocation through the plasma membrane, while A-B frag-merit retains enzymatic activity [2].…”

Section: Introductionmentioning

confidence: 99%

Tetanus toxin selectively impairs anti-tumoral but not anti-microbial macrophage-mediated effector functions

Pitzurra

1993

FEMS Immunology and Medical Microbiology

View full text Add to dashboard Cite

The present study was designed to establish the susceptibility of macrophage-mediated effector functions to tetanus toxin (TT). Using the murine macrophage cell line, GG2EE, generated in vitro by v-raf/v-myc oncogenes, we have previously provided evidence that TT selectively inhibits interferon gamma (IFN-gamma), but not basal, lysozyme activity. Here we show that while neither phagocytic nor candidacidal activities are affected by TT treatment, antitumoral activity is significantly impaired after exposure to TT. This phenomenon, which is dose-dependent, is fully ascribed to the holotoxin, as heat inactivated TT, C or A-B fragments result ineffective. Furthermore, C but not A-B fragment competes with TT in abrogating its inhibitory effects. Overall, these data indicate that TT is not a broad-spectrum, down-regulating signal on macrophage-mediated functions, thus implying that its toxic action is exerted on specific molecular targets.

show abstract

“…These toxins are structurally homologous [4][5][6][7][8]. Both are aqueous soluble proteins with an apparent Mr --150,000.…”

Section: Introductionmentioning

confidence: 99%

“…They are formed from two disulfide-linked chains: the light chain with M~ = 50,000 and the heavy chain, Mr = 100,000. Proteolytic cleavage, produces three distinct fragments [4], A, B and C. A is the light chain, B is a proteolytic fragment of the heavy chain, the N-terminal half with M r = 50,000 known asp2 and H2 for TeTx and BoTxA, respectively, and C is the Cterminal half of the heavy chain with Mr = 50,000, known as fragment C and H1 for TeTx and BoTxA, respectively [4,9].…”

Section: Introductionmentioning

confidence: 99%

Identification of an ion channel‐forming motif in the primary structure of tetanus and botulinum neurotoxins

et al. 1992

View full text Add to dashboard Cite

Synthetic peptides with amino acid ~eqttences corresponding to predicted transmembran¢ segments of tet~tntts toxin were used as probes to identify a elmnnel-forming motif. A peptide denoted TeTx 1I. with sequence GVVLLLEYIPEITLPVIAALSIA, form.~ cation-selective channels when r~onztltuted in planar lipid bilaycrz. The .~ia~le channel conductance in 0.~ M NaCI or KCI is 28 + 3 ~tnd 24 ± 2 pS. respectively. In contrast, a peptide with sequence NFIGALETTGVVLLLEYIPEIT. denoted as TeTx I. or a peptide with the mine amino acid composition as TeTx II but with a randomized ~eqaence, do not form channels. Conformational enersy calculations show that a baladle of four amphipathic a-helices is a plausible structural motif underlying observable pore properties. The identified functional module may account for the channel-forming activity of both tetanus toxin ~md the hom~losous botulinum to~in A.

show abstract

Tetanus toxin.

Cited by 73 publications

References 56 publications

Solid‐phase synthesis, conformational analysis and in vitro cleavage of synthetic human synaptobrevin II 1–93 by tetanus toxin L chain

Solid‐phase synthesis, conformational analysis and in vitro cleavage of synthetic human synaptobrevin II 1–93 by tetanus toxin L chain

Tetanus toxin selectively impairs anti-tumoral but not anti-microbial macrophage-mediated effector functions

Identification of an ion channel‐forming motif in the primary structure of tetanus and botulinum neurotoxins

Contact Info

Product

Resources

About