The isolation and some properties of the major neurotoxic component from the venom of the common or Eastern Australian brown snake (Pseudonaja textilis)

Coulter, A.R.; Harris, R.D.; Broad, A.J.; Sutherland, Struan K.; Sparrow, Lindsay G.; Misconi, Lutfi; Hamilton, R. C.; Rubira, Michael R.

doi:10.1016/0041-0101(83)90160-5

Cited by 16 publications

(8 citation statements)

References 17 publications

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“…The apparent lack of myotoxicity of the venom has been confirmed in the monkey by Sutherland & Campbell (1980) but the apparent lack of presynaptic activity is possibly contentious. Coulter, Broad & Sutherland (1980) have isolated a high molecular weight protein (textilon) from the crude venom of Pseudonaja textilis, and preliminary studies by Southcott & Coulter (1980) have suggested that it is a presynaptically active neurotoxin. If this is so, the apparent lack of such activity in the crude venom presumably reflects the overriding potency of the postsynaptically active fractions.…”

Section: Discussionmentioning

confidence: 99%

THE EFFECTS OF THE SUBCUTANEOUS INJECTION OF THE CRUDE VENOM OF THE AUSTRALIAN COMMON BROWN SNAKE, Pseudonaja textilis ON THE SKELETAL NEUROMUSCULAR SYSTEM

Harris

Maltin

1981

British J Pharmacology

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The effects of the crude venom of the Australian common brown snake on the mammalian neuromuscular system have been investigated. The venom was injected subcutaneously into the dorso‐lateral aspect of one hind limb of the rat. The limb was paralysed within 90 min and remained paralysed for 2 to 3 days. The exposed muscles failed to respond to indirect excitation, and individual fibres were not depolarized at the nerve‐muscle junction by exposure to carbachol. The wet weight, histological appearance, resting potential and input resistance of the muscle fibres and their ability to generate directly elicited action potentials were unaffected by exposure to the venom. Administration of venom to isolated preparations caused a reduction in the amplitude of miniature endplate potentials, with no change in frequency. The quantal content of evoked endplate potentials was unchanged. It was concluded that the crude venom was largely devoid of presynaptic activity and myotoxicity, and that its primary site of neurotoxicity was directed to the postsynaptic membrane.

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Section: Discussionmentioning

confidence: 99%

THE EFFECTS OF THE SUBCUTANEOUS INJECTION OF THE CRUDE VENOM OF THE AUSTRALIAN COMMON BROWN SNAKE, Pseudonaja textilis ON THE SKELETAL NEUROMUSCULAR SYSTEM

Harris

Maltin

1981

British J Pharmacology

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“…It has recently been postulated that this family of snakes (Elapidae) have utilized protein oligomerization as an effective evolutionary tool to improve the effectiveness, hence lethality of their toxins 4 . The most recent study into the subunit sequence and stoichiometry of textilotoxin was published some 15 years ago 3 , with the earliest data appearing in 1983 5 . Coulter et al (1983) observed either a pentamer or hexamer, depending on the method of analysis used.…”

Section: Introductionmentioning

confidence: 99%

“…The most recent study into the subunit sequence and stoichiometry of textilotoxin was published some 15 years ago 3 , with the earliest data appearing in 1983 5 . Coulter et al (1983) observed either a pentamer or hexamer, depending on the method of analysis used. Subsequent studies have assumed, based purely on the number subunits which can be purified, that textilotoxin is pentameric 2,3,6 , consisting of subunits A, B, C and a D 2 dimer.…”

Section: Introductionmentioning

confidence: 99%

The major toxin from the Australian Common Brown Snake is a hexamer with unusual gas‐phase dissociation properties

Aquilina

2008

Proteins

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Asymmetric dissociation of multiply charged protein assemblies has been frequently reported. This phenomenon, which relies on the dissociation of one or more highly charged monomers, has been shown to provide insights into the structure and organization of large monodisperse and polydisperse assemblies. Here, the process of asymmetric dissociation is investigated using the multisubunit protein, textilotoxin, which has unusually high structural constraints on its monomers due to multiple disulfide linkages. Initially, it is shown that, contrary to previous reports, textilotoxin is made up of six, rather than five subunits. Furthermore, the hexamer exists as two isoforms, one of which is substantially more glycosylated. Gas-phase dissociation studies on the hexamers reveal the subunit stoichiometry of each isoform to be (A/B)(2)C(2)D(2a) and (A/B)CD(2a)D(2b), where A and B are subunits of very similar mass and D(2a), D(2b) refer to differentially glycosylated dimers of the D subunit. The mechanism of dissociation was unusual, as rather than one subunit being largely removed before sequential dissociation of a second, the process was predominantly concurrent for the two smallest subunits. Furthermore, a small proportion of the dissociated species was observed to be a noncovalently associated dimer. A comparison of dissociation pathways for two neighboring charge states of the same textilotoxin isoform demonstrates that, in agreement with previous reports, variations in quaternary structure are responsible for the distinct charge states of a protein.

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“…Four fractions were collected by monitoring the eluate at 280 nm and two of these fractions were found to be toxic by intraperitoneal injection in white mice. Fraction 2 (20.3 mg) contained textilotoxin [4,5] and fraction 3 (51.5 mg) contained pseudonajatoxin b. The column was re-run several times with similar amounts of venom under the same conditions (Supplement Fig.…”

Section: Gel Filtrationmentioning

confidence: 99%

Pseudonajatoxin b: unusual amino acid sequence of a lethal neurotoxin from the venom of the Australian common brown snake, Pseudonaja textilis

Tyler

Spence²,

Barnett

et al. 1987

Eur J Biochem

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The complete amino acid sequence of pseudonajatoxin b, a basic neurotoxin from the venom of the Australian common brown snake, Pseudonuju textilis, was determined by automated Edman analysis of the reduced carboxymethylated polypeptide and of peptides derived by digestion of it with Staphylococcus aureus V8 proteinase. Pseudonajatoxin b consists of a single polypeptide chain of 71 amino acids with M , 7762. The amino acid sequence showed considerable homology with postsynaptic long neurotoxins, but there were striking differences. Pseudonajatoxin b displayed relatively high lethality, LDS0 15 pg/kg in mice.Although recent studies [l] have advanced greatly our knowledge of the structure of the acetylcholine-receptorionophore complex our understanding of the different conformations in situ has not advanced so rapidly. It is well known from studies with pharmacological agents that in different membranes it (or they) adopt different conformations. These differences may be marked, as between the nicotinic and muscarinic conformations, or more subtle as between the conformation in the skeletal muscle and in autonomic ganglia.One approach to studying these differences in in situ conformation is to examine the three-dimensional structure of acetylcholine receptor antagonists. Recent advances in the isolation and characterization of snake neurotoxins indicate that these may prove to be useful in studies of this question [2]. Most of the toxins isolated so far, however, show affinity only for the skeletal muscle acetylcholine receptor [2]. Recently, however, a new neurotoxin, K--bungarotoxin, from the venom of the snake Bungarus multicinctus was isolated which showed no affinity for these receptors but blocked the acetylcholine receptor on sympathetic ganglia [3].In the present study we report the isolation, amino acid sequence determination and preliminary pharmacology of a novel snake neurotoxin, pseudonajatoxin b, which was isolated from the venom of the Australian common brown snake Pseudonaja textilis. A postsynaptic neurotoxin pseudonajatoxin a [4], and a presynaptic neurotoxin, textilotoxin [4, 51 from the venom of the same snake, have been described, but their structures have not been fully determined. MATERIALS AND METHODS Venom Box 64, Cooktown, Australia).The venom was purchased from Mr Charles Tanner (P. Animals used for lethality tests were adult female Swiss Gel filtrationCrude venom (100 mg) was dissolved in 2 mlO.1 M ammonium acetate pH 6.5 and applied to a column of Ultrogel AcA 44. Four fractions were collected by monitoring the eluate at 280 nm and two of these fractions were found to be toxic by intraperitoneal injection in white mice. Fraction 2 (20.3 mg) contained textilotoxin [4,5] and fraction 3 (51.5 mg) contained pseudonajatoxin b. The column was re-run several times with similar amounts of venom under the same conditions (Supplement Fig. 1). Ion-exchange high-performunee liquid chromatographyFraction 3 from the Ultrogel AcA 44 column was dissolved in 0.025 M ammonium acetate pH 5.5 and applied ...

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The isolation and some properties of the major neurotoxic component from the venom of the common or Eastern Australian brown snake (Pseudonaja textilis)

Cited by 16 publications

References 17 publications

THE EFFECTS OF THE SUBCUTANEOUS INJECTION OF THE CRUDE VENOM OF THE AUSTRALIAN COMMON BROWN SNAKE, Pseudonaja textilis ON THE SKELETAL NEUROMUSCULAR SYSTEM

THE EFFECTS OF THE SUBCUTANEOUS INJECTION OF THE CRUDE VENOM OF THE AUSTRALIAN COMMON BROWN SNAKE, Pseudonaja textilis ON THE SKELETAL NEUROMUSCULAR SYSTEM

The major toxin from the Australian Common Brown Snake is a hexamer with unusual gas‐phase dissociation properties

Pseudonajatoxin b: unusual amino acid sequence of a lethal neurotoxin from the venom of the Australian common brown snake, Pseudonaja textilis

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