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Clostridial Neurotoxins pp 257–274Cite as

Intracellular Targets and Metalloprotease Activity of Tetanus and Botulism Neurotoxins

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 195))

Abstract

Tetanus and botulism neurotoxins (TeNT and BoNT, respectively) produced by Clostridia are the most toxic substances known: the mouse LD50 of highly purified preparations is between 0.1 and 1 ng/kg. They block the release of neuro- transmitters either at the peripheral (BoNT) or central (TeNT) nervous system. This tremendous potency derives from two essential features of these bacterial toxins: (a) their absolute neurospecificity and (b) their intracellular catalytic activity. By concentrating their action on a limited number of cells, whose complete functionality is essential to the survival of very complex animals such as the vertebrates, neurotoxins lead to animal death with a minimal amount of toxic molecules. The basis of this cell selectivity resides on receptors uniquely present on neuronal cells (see Halpern and Neale, this volume). Although questioned by a number of researchers, it was not unexpected that clostridial neurotoxins are enzymes, acting in the neuron cytosol (Schiavo et al. 1993a). In fact, an enzyme can modify one after another all the target molecules present in the system and hence one single molecule of an enzymic toxin is able to intoxicate a synapse. TeNT and the seven BoNTs, A-G, are zinc endopeptidases specific for protein components of the neuroexocytosis apparatus. This enzymatic activity is the subject of this chapter.

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References

  • Allured VA, Collier RJ, Carroll SF, McKay DB (1986) Structure of exotoxin A from Pseudomonas aeruginosa at 3.0 Angstrom resolution. Proc Natl Acad Sci USA 83: 1320–1324

    Article  PubMed  CAS  Google Scholar 

  • Anderson MD, Fairweather N, Charles IG, Emsley PJsaacs NW, MacDermott G (1993) Crystallographic characterization of tetanus toxin fragment C. J Mol Biol 230: 673–674

    Article  PubMed  CAS  Google Scholar 

  • Archer BT, Ozcelik T, Jahn R, Francke U, Südhof TC (1990) Structures and chromosomal localizations of two human genes encoding synaptobrevins 1 and 2. J Biol Chem 265: 17267–17273

    PubMed  CAS  Google Scholar 

  • Ashton AC, de Paiva AM, Poulain B, Taue L, Dolly JO (1993) Factors underlying the characteristics inhibition of the neuronal release of transmitters by tetanus and various botulinum toxin. In: DasGupta BR (ed) Botulinum and tetanus neurotoxins, neurotransmission and biomedical aspects. Plenum, New York, pp 191–213

    Google Scholar 

  • Bark C (1993) Structure of the chicken gene for SNAP-25 reveals duplicated exons encoding distinct isoforms of the protein. J Mol Biol 233: 67–76

    Article  PubMed  CAS  Google Scholar 

  • Bark C (1994a) Regulated vesicular fusion in neurons: snapping together the details. Proc Natl Acad Sci USA 91: 4621–4624

    Article  PubMed  CAS  Google Scholar 

  • Bark C, Wilson MC (1994b) Human cDNA clones encoding two different isoforms of the nerve terminal protein SNAP-25. Gene 139: 291–292

    Article  PubMed  CAS  Google Scholar 

  • Bartels F, Bergel H, Bigalke H, Frevert J, Halpern J, Middlebrook JL (1994) Specific antibodies against the Zn-binding domain of clostridial neurotoxins restore exocytosis in chromaffin cells treated with tetanus or botulinum A neurotoxin. J Biol Chem 269: 8122–8127

    PubMed  CAS  Google Scholar 

  • Baumann U, Wu S, Flaherty KM, McKay DB (1993) Three-dimensional structure of the alkaline protease of Pseudomonas aeruginosa: a two domain protein with a calcium binding parallel beta roll motif. EMBO J 12: 3357–3364

    PubMed  CAS  Google Scholar 

  • Baumert M, Maycox PR, Navone F, De Camilli P, Jahn R (1989) Synaptobrevin: an integral membrane protein of 18 000 daltons present in small synaptic vesicles of rat brain. EMBO J 8: 379–384

    PubMed  CAS  Google Scholar 

  • Bennett MK, Scheller RH (1994) A molecular description of synaptic vesicle membrane trafficking. Annu Rev Biochem 63: 63–100

    Article  PubMed  CAS  Google Scholar 

  • Bennett MK, Calakos N, Scheller RH (1992) Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science 257: 255–259

    Article  PubMed  CAS  Google Scholar 

  • Bennett MK, Garcia-Arras JE, Elferink LA, Peterson K, Fleming AM, Hazuka CD, Scheller RH (1993) The syntaxin family of vesicular transport receptors. Cell 74: 863–873

    Article  PubMed  CAS  Google Scholar 

  • Binz T, Blasi J, Yamasaki S, Baumeister A, Link E, Südhof TC, Jahn R, Niemann H (1994) Proteolysis of SNAP-25 by types E and A botulinal neurotoxins. J Biol Chem 269: 1617–1620

    PubMed  CAS  Google Scholar 

  • Blasi J, Chapman ER, Link E, Binz T, Yamasaki S, DeCamilli P, Südhof T, Niemann H, Jahn R (1993a) Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25. Nature 365: 160–163

    Article  PubMed  CAS  Google Scholar 

  • Blasi J, Chapman ER, Yamasaki S, BinzT, Niemann H, Jahn R (1993b) Botulinum neurotoxin C blocks neurotransmitter release by means of cleaving HPC-1/syntaxin. EMBO J 12: 4821–4828

    PubMed  CAS  Google Scholar 

  • Bode W, Gomis-Ruth FX, Huber R, Zwilling R, Stocker VV (1992) Structure of astacin and implication of astacins and zinc-ligation of collagenases. Nature 358: 164–166

    Article  PubMed  CAS  Google Scholar 

  • Bode W, Gomis-Ruth FX, Stocker VV (1993) Astacins, serralysin, snake venoms and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the “metzincins.” FEBS Lett 331: 134–140

    Article  PubMed  CAS  Google Scholar 

  • Bode W, Reinemer P, Huber R, Kleine T, Schnierer S, Tschesche H (1994) The X-ray crystal structure of the catylytic domain of human neutrophil collagenase inhibited by a substrate analogue reveals the essentials for catalysis and specificity. EMBO J 13: 1263–1269

    PubMed  CAS  Google Scholar 

  • Braun JEA, Fritz BA, Wong SME, Lowe AW (1994) Identification of a vesicle-associated membrane protein (VAMP-like) membrane protein in zymogen granules of the rat exocryne pancreas. J Biol Chem 269: 5328–5335

    PubMed  CAS  Google Scholar 

  • Chin AC, Burgess RW, Wong BR, Schwarz TL, Scheller RH (1994) Differential expression of transcripts from syb, a Drosophila melanogaster gene encoding VAMP (synaptobrevin that is abundant in nonneuronal cells. Gene 131: 175–181

    Article  Google Scholar 

  • Choe S, Bennett MJ, Fujii G, Curmi PMG, Kantardjieff KA, Collier RJ, Eisenberg D (1992) The crystal structure of diphtheria toxin. Nature 367: 216–222

    Article  Google Scholar 

  • Corley Cain C, Trimble WS, Leinhard GE (1992) Members of the VAMP family of synaptic vesicles proteins are components of glucose transporter-containing vesicles from rat adipocytes. J Biol Chem 267: 11681–11684

    Google Scholar 

  • DasGupta BR (1989) The structure of botulinum neurotoxin. In: Simpson LL (ed) Botulinum neurotoxins and tetanus toxin. Academic, New York, pp 53–67

    Google Scholar 

  • Dayanithi G, Stecher B, Höhne-Zell B, Yamasaki S, Binz T, Weiler U, Niemann H, Gratzl M (1994) Exploring the functional domain and the target of the tetanus toxin light chain in neurohypophysial terminals. Neuroscience 58: 423–431

    Article  PubMed  CAS  Google Scholar 

  • de Paiva A, Poulain B, Lawrence GW, Shone CC, Taue L, Dolly JO (1993a) A role for the interchain disulfide or its participating thiols in the internalization of botulinum neurotoxin A revealed by a toxin derivative that binds to ecto-acceptors and inhibits transmitter release intracellularly. J Biol Chem 268: 20838–20844

    PubMed  Google Scholar 

  • de Paiva A, Ashton AC, Foran P, Schiavo G, Montecucco C, Dolly JO (1993b) Botulinum A like type B and tetanus toxin fulfils criteria for being a zinc-dependent protease. J Neurochem 61: 2338–2341

    Article  PubMed  Google Scholar 

  • DiAntonio A, Burgess RW, Chin AC, Deitcher DL, Scheller RH, Schwarz TL (1993) Identification and characterization of Drosophila genes for synaptic vesicle proteins. J Neurosci 13: 4924–4935

    PubMed  CAS  Google Scholar 

  • Elferink LA, Trimble WS, Scheller RH (1989) Two vesicle-associated membrane protein genes are differently expressed in the rat central nervous system. J Biol Chem 264: 11061–11064

    PubMed  CAS  Google Scholar 

  • Gomis-Ruth FX, Kress LF, Bode W (1993) First structure of a snake venom metalloproteinase: a prototype for matrix metalloproteinases/collagenases. EMBO J 12: 4151–4157

    PubMed  CAS  Google Scholar 

  • Hess TS, Slater TM, Wilson MC, Skene JHP (1992) The 25 kDa synaptosomal-associated protien SNAP-25 is the major methionine-rich polypeptide in rapid axonal transport and a major substrate for palmitoylation in adult CNS. J Neurosci 12: 4634–4641

    PubMed  CAS  Google Scholar 

  • Höhne-Zell B, Stecher B, Gratzl M (1993) Functional characterization of the catalytic site of the tetanus toxin light chain using permeabilized adrenal chromaffin cells. FEBS Lett 336: 175–180

    Article  PubMed  Google Scholar 

  • Hunt JM, Bommert K, Charlton MP, Kistner A, Habermann E, Augustine GJ, Betz H (1994) A post-docking role for synaptobrevin in synaptic vesicle fusion. Neuron 12: 1269–1279

    Article  PubMed  CAS  Google Scholar 

  • Inoue A, Obata K, Akagawa K (1992) Cloning and sequence analysis of cDNA for a neuronal cell membrane antigen, HPC-1. J Biol Chem 267: 10613–10619

    PubMed  CAS  Google Scholar 

  • Jiang W, Bond JS (1992) Families of metalloendopeptidases and their relationships. FEBS Lett 312: 110–114

    Article  PubMed  CAS  Google Scholar 

  • Jongeneel CV, Bouvier J, Bairoch A (1989) A unique signature identifies a family of zinc-dependent metallopeptidases. FEBS Lett 242: 211–214

    Article  PubMed  CAS  Google Scholar 

  • Krieglstein KG, Henschen A, Weiler U, Habermann E (1991) Limited proteolysis of tetanus toxin. Eur J Biochem 202: 41–51

    Article  PubMed  CAS  Google Scholar 

  • Link E, Edelmann L, Chou JH, Binz T, Yamasaki S, Eisel U, Baumert M, Südhof TC, Niemann H, Jahn R (1992) Tetanus toxin action: inhibition of neurotransmitter release linked to synaptobrevin proteolysis. Biochem Biophys Res Commun 189: 1017–1023

    Article  PubMed  CAS  Google Scholar 

  • Lovejoy B, Cleasby A, Hassell AM, Longley K, Luther MA, Weigl D, McGeehan G, McElroy AB, Drewry D, Lambert MH, Jordan SR (1994) Structure of the catalytic domain of fibroblast collagenase complexed with an inhibitor. Science 263: 375–377

    Article  PubMed  CAS  Google Scholar 

  • Matthews BW (1988) Structural basis of the action of thermolysin and related zinc peptidases. Acc Chem Res 21: 333–340

    Article  CAS  Google Scholar 

  • Matthews BW, Jansonius JN, Colman PM (1972) Three-dimensional structure of thermolysin. Nature New Biol 238: 37–41

    Article  PubMed  CAS  Google Scholar 

  • McMahon HT, Ushkaryov YA, Edelmann L, Link E, Binz T, Niemann H, Jahn R, Südhof TC (1993) Cellubrevin is a ubiquitous tetanus-toxin substrate homologous to a putative synaptic vesicle fusion protein. Nature 364: 346–349

    Article  PubMed  CAS  Google Scholar 

  • Miles EW (1977) Modification of histidyl residues in proteins by diethylcarbonate. Methods Enzymol 47: 431–442

    Article  PubMed  CAS  Google Scholar 

  • Montecucco C, Schiavo G (1993) Tetanus and botulism neurotoxins: a new group of zinc proteases. Trends Biochem Sci 18: 324–327

    Article  PubMed  CAS  Google Scholar 

  • Montecucco C, Schiavo G (1994) The molecular mechanism of action of tetanus and botulism neurotoxins. Mol Microbiol 13: 1–8

    Article  PubMed  CAS  Google Scholar 

  • Montecucco C, Papini E, Schiavo G (1994) Bacterial protein toxins penetrate cells via a four-step mechanism. FEBS Lett 346: 92–98

    Article  PubMed  CAS  Google Scholar 

  • Niemann H (1991) Molecular biology of clostridial neurotoxins. In: Alouf JE, Freer JH (eds) A sourcebook of bacterial protein toxins. Academic, London, pp 303–348

    Google Scholar 

  • Nishiki T, Kamata Y, Nemoto Y, Omori A, Ito T, Takahashi M, Kozaki S (1994) Identification of protein receptor for Clostridium botulinum type B neurotoxin in rat brain synaptosomes. J Biol Chem 269: 10498–10503

    PubMed  CAS  Google Scholar 

  • Osen-Sand A, Catsicas M, Staple JK, Jones KA, Ayala G, Knowles J, Grenningloh G, Catsicas S (1993) Inhibition of axonal growth by SNAP-25 antisense oligonucleotides in vitro and in vivo. Nature 364: 445–448

    Article  PubMed  CAS  Google Scholar 

  • Oyler GA, Higgins GA, Hart RA, Battenberg E, Billingsley M, Bloom FE, Wilson MC (1989) The identification of a novel synaptosomal-associated protein, SNAP-25, differently expressed by neuronal subpopulations. J Cell Biol 109: 3039–3052

    Article  PubMed  CAS  Google Scholar 

  • Patamello T, Bargelloni L, Rossetto O, Schiavo G, Montecucco C (1993) Neurotransmission and secretion. Nature 364: 581–582

    Article  Google Scholar 

  • Pauptit RA, Karlsson R, Picot D, Jenkins JA, Niklaus-Reimer AS, Jansonius JN (1988) Crystal structure of neutral protease from Bacillus cereus refined at 3.0 A resolution and comparison with the homologous but more thermostable enzyme termolysin. J Mol Biol 199: 525–537

    Article  PubMed  CAS  Google Scholar 

  • Payling-Wright G (1955) The neurotoxins of Clostridium botulinum and Clostridium tetani. Pharmacol Rev 7: 413–465

    Google Scholar 

  • Poulain B, Rossetto O, Deloye F, Schiavo G, Taue L, Montecucco C (1993) Antibodies against rat brain vesicle-associated membrane protein (sinaptobrevin) prevent inhibition of acetylcholine release by tetanus toxin of botulinum neurotoxin type B. J Neurochem 61: 1175–1178

    Article  PubMed  CAS  Google Scholar 

  • Ralston E, Beushausen S, Ploug T (1994) Expression of the synaptic vesicle proteins VAMPs/synaptobrevins 1 and 2 in non-neuronal tissue. J Biol Chem 269: 15403–15406

    PubMed  CAS  Google Scholar 

  • Risinger C, Larhammar D (1993) Multiple loci for synapse protein SNAP-25 in the tetraploid goldfish. Proc Natl Acad Sci USA 90: 10598–10602

    Article  PubMed  CAS  Google Scholar 

  • Risinger C, Blomqvist AG, Lundell I, Lambertsson A, Nässel D, Pierbone VA, Brodin L, Larhammar D (1993) Evolutionary conservation of synaptosome-associated protein 25 kDa (SNAP-25) shown by Drosophila and Torpedo cDNA clones. J Biol Chem 268: 24408–24414

    PubMed  CAS  Google Scholar 

  • Robinson JP, Schmid MF, Morgan DG, Chiu VV (1988) Three-dimensional structural analysis of tetanus toxin by electron crystallography. J Mol Biol 200: 367–375

    Article  PubMed  CAS  Google Scholar 

  • Rossetto O, Schiavo G, Polverino de Laureto P, Fabbiani S, Montecucco C (1992) Surface topography of histidine residues of tetanus toxin probed by immobilized-metal-ion affinity chromatography. Biochem J 285: 9–12

    PubMed  CAS  Google Scholar 

  • Rossetto O, Gorza L, Schiavo G, Schiavo N, Neale EA, Scheller RH, Montecucco C (1994) VAMP/synaptobrevin neuronal isoforms are ubiquitous and play a role additional to vesicle docking. (submitted)

    Google Scholar 

  • Rothman JE, Warren G (1994) Implications of the SNARE hypothesis for intracellular membrane topology and dynamics. Curr Biol 4: 220–233

    Article  PubMed  CAS  Google Scholar 

  • Sadoul K, Lang J, Montecucco C, Weller U, Catsicas S, Wollheim C, Halban P (1994) SNAP-25 is expressed in islets of Langerhans and is involved in insulin release. J Cell Biol (in press)

    Google Scholar 

  • Schiavo G, Montecucco C (1994) Tetanus and botulism neurotoxins: isolation and assay. Methods Enzymol (in press)

    Google Scholar 

  • Schiavo G, Papini E, Genna G, Montecucco C (1990) An intact interchain disulfide bond is required for the neurotoxicity of tetanus toxin. Infect Immun 58: 4136–4141

    PubMed  CAS  Google Scholar 

  • Schiavo G, Poulain B, Rossetto O, Benfenati F, Taue L, Montecucco C (1992a) Tetanus toxin is a zinc protein and its inhibition of neurotransmitter release and protease activity depend on zinc. EMBO J 11: 3577–3583

    PubMed  CAS  Google Scholar 

  • Schiavo G, Benfenati F, Poulain B, Rossetto O, Polverino de Laureto P, DasGupta BR, Montecucco C (1992b) Tetanus and botulinum-B neurotoxins of block neurotransmitter release by a proteolytic cleavage of synaptobrevin. Nature 359: 832–835

    Article  PubMed  CAS  Google Scholar 

  • Schiavo G, Rossetto O, Santucci A, DasGupta BR, Montecucco C (1992c) Botulinum neurotoxins are zinc proteins. J Biol Chem 267: 23479–23483

    PubMed  CAS  Google Scholar 

  • Schiavo G, Poulain B, Benfenati F, DasGupta BR, Montecucco C (1993a) Novel targets and catalytic activities of bacterial protein toxins. Trends Microbipl 1: 170–174

    Article  CAS  Google Scholar 

  • Schiavo G, Shone CC, Rossetto O, Alexandre FCG, Montecucco C (1993b) Botulinum neurotoxin serotype F is a zinc endopeptidase specific for VAMP/synaptobrevin. J Biol Chem 268: 11516–11519

    PubMed  CAS  Google Scholar 

  • Schiavo G, Rossetto O, Catsicas S, Polverino de Laureto P, DasGupta BR, Benfenati F, Montecucco C (1993c) Identification of the nerve-terminal targets of botulinum neurotoxins serotypes A, D and E. J Biol Chem 268: 23784–23787

    PubMed  CAS  Google Scholar 

  • Schiavo G, Santucci A, DasGupta BR, Metha PP, Jontes J, Benfenati F, Wilson MC, Montecucco C (1993d) Botulinum neurotoxins serotypes A and E cleave SNAP-25 at distinct COOH-terminal peptide bonds. FEBS Lett 335: 99–103

    Article  PubMed  CAS  Google Scholar 

  • Schiavo G, Rossetto O, Benfenati F, Poulain B, Montecucco C (1994a) Tetanus and botulinum neurotoxins are zinc proteases specific for components of the neuroexocytosis apparatus. Ann NY Acad Sci 710: 65–75

    Article  PubMed  CAS  Google Scholar 

  • Schiavo G, Malizio C, Trimble WS, Polverino de Laureto P, Milan G, Sugiyama H, Johnson EA, Montecucco C (1994b) Botulinum G neurotoxin cleaves VAMP/synaptobrevin at a single Ala/Ala peptide bond. J Biol Chem 269: 20213–20216

    PubMed  CAS  Google Scholar 

  • Schiavo G, Shone CC, Bennett MK, Scheller RH, Montecucco C (1994c) Botulinum neurotoxin type C cleaves a single Lys-Ala bond within the carboxyl-terminal region of syntaxin. J Biol Chem 270 (in press)

    Google Scholar 

  • Shone CC, Quinn CP, Wait R, Hallis B, Fooks SG, Hambleton P (1993) Proteolytic cleavage of synthetic fragments of vesicle-associated membrane protein, isoform-2 by botulinum type B neurotoxin. Eur J Biochem 217: 965–971

    Article  PubMed  CAS  Google Scholar 

  • Söllner T, Whiteheart SW, Brunner M, Erdjument-Bromage H, Geromanos S, Tempst P, Rothman JE (1993a) SNAP receptors implicated in vesicle targeting and fusion. Nature 362: 318–324

    Article  PubMed  Google Scholar 

  • Söllner T, Bennett M, Whiteheart SW, Scheller RH, Rothman JE (1993b) A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. Cell 75: 409–418

    Article  PubMed  Google Scholar 

  • Steinhardt RA, Bi G, Alderton JM (1994) Cell membrane resealing by a vesicular mechanism similar to neurotransmitter release. Science 263: 390–393

    Article  PubMed  CAS  Google Scholar 

  • Stevens RC, Evenson ML, Tepp W, DasGupta BR (1991) Crystallization and preliminary X-ray analysis of botulinum neurotoxin type A. J Mol Biol 222: 877–880

    Article  PubMed  CAS  Google Scholar 

  • Südhof TC, Baumert M, Perin MS, Jahn R (1989) A synaptic vesicle membrane protein is conserved from mammals to Drosophila. Neuron 2: 1475–1481

    Article  PubMed  Google Scholar 

  • Thayer MM, Flaherty KM, McKay DB (1991) Three-dimensional structure of the elastase of Pseudomonas aeruginosa at 1.5 A resolution. J Biol Chem 266: 2864–2871

    PubMed  CAS  Google Scholar 

  • Trimble WS, Cowan DM, Scheller RH (1988) VAMP-1: a synaptic vesicle-associated integral membrane protein. Prot Natl Acad Sci USA 85: 4538–4542

    Article  CAS  Google Scholar 

  • Trimble WS, Linial M, Scheller RH (1991) Cellular and molecular biology of the presynaptic nerve terminal. Annu Rev Neurosci 14: 93–122

    Article  PubMed  CAS  Google Scholar 

  • Vallée BL, Auld DS (1990) Zinc coordination, function and structure of zinc enzymes and other proteins. Biochemistry 29: 5647–5659

    Article  PubMed  Google Scholar 

  • Wanke E, Ferroni A, Gattanini P, Meldolesi J (1986) Alpha-latratoxin of the black widow spider venom opens small, non-closing cation channel. Biochem Biophys Res Commun 134: 320–325

    Article  PubMed  CAS  Google Scholar 

  • Wellhoner HH (1992) Tetanus and botulinum neurotoxins. In: Herken H, Hucho F (eds) Handbook of experimental pharmacology, vol 102. Springer, Berlin Heidelberg New York, pp 357–417

    Google Scholar 

  • Wright JF, Pemollet M, Reboul A, Aude C, Colomb M (1992) Identification and partial characterization of a low affinity metal-binding site in the light chain of tetanus toxin. J Biol Chem 267: 9053–9058

    PubMed  CAS  Google Scholar 

  • Yamasaki S, Hu Y, Binz T, Kalkuhl A, Kurazono H, Tamura T, Jahn R, Kandel E, Niemann H (1994a) Synaptobrevin/VAMP of Aplysia californica: structure and proteolysis by tetanus and botulinal neurotoxins type D and F. Proc Natl Acad Sci USA 91: 4688–4692

    Article  PubMed  CAS  Google Scholar 

  • Yamasaki S, Baumeister A, Binz T, Blasi J, Link E, Cornille F, Roques B, Fykse EM, Südhof TC, Jahn R, Niemann H (1994b) Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin. J Biol Chem 269: 12764–12772

    PubMed  CAS  Google Scholar 

  • Yamasaki S, Binz T, Hayashi T, Szabo E, Yamasaki N, Eklund M, Jahn R, Niemann H (1994c) Botulinum neurotoxin type G proteolyses the Ala81-Ala82 bond of rat synaptobrevin 2. Biochem Biophys Res Commun 200: 829–835

    Article  PubMed  CAS  Google Scholar 

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  1. Centra CNR Biomembrane and Dipartimento di Scienze Biomediche, Università di Padova, Via Trieste 75, 35121, Padova, Italy

    G. Schiavo, O. Rossetto, F. Tonello & C. Montecucco

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  1. G. Schiavo
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  2. O. Rossetto
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  3. F. Tonello
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  1. Dipartimento di Scienze Biomediche Sperimentali, Università degli Studi di Padova, Via Trieste, 75, 35121, Padova, Italia

    Cesare Montecucco

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Schiavo, G., Rossetto, O., Tonello, F., Montecucco, C. (1995). Intracellular Targets and Metalloprotease Activity of Tetanus and Botulism Neurotoxins. In: Montecucco, C. (eds) Clostridial Neurotoxins. Current Topics in Microbiology and Immunology, vol 195. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-85173-5_12

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