Isolation of δ-missulenatoxin-Mb1a, the major vertebrate-active spider δ-toxin from the venom of Missulena bradleyi (Actinopodidae)

Gunning, SJ; Chong, Y; Khalife, AA; Hains, PG; Broady, KW; Nicholson, GM

Isolation of δ-missulenatoxin-Mb1a, the major vertebrate-active spider δ-toxin from the venom of Missulena bradleyi (Actinopodidae)

Gunning, SJ Chong, Y Khalife, AA Hains, PG Broady, KW Nicholson, GM

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Publication Type:: Journal Article
Citation:: FEBS Letters, 2003, 554 (1-2), pp. 211 - 218
Issue Date:: 2003-11-06

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Field	Value	Language
dc.contributor.author	Gunning, SJ	en_US
dc.contributor.author	Chong, Y	en_US
dc.contributor.author	Khalife, AA	en_US
dc.contributor.author	Hains, PG	en_US
dc.contributor.author	Broady, KW	en_US
dc.contributor.author	Nicholson, GM https://orcid.org/0000-0002-4277-4296	en_US
dc.date.issued	2003-11-06	en_US
dc.identifier.citation	FEBS Letters, 2003, 554 (1-2), pp. 211 - 218	en_US
dc.identifier.issn	0014-5793	en_US
dc.identifier.uri	http://hdl.handle.net/10453/3837
dc.description.abstract	The present study describes the isolation and pharmacological characterisation of the neurotoxin δ-missulenatoxin-Mb1a (δ-MSTX-Mb1a) from the venom of the male Australian eastern mouse spider, Missulena bradleyi. This toxin was isolated using reverse-phase high-performance liquid chromatography and was subsequently shown to cause an increase in resting tension, muscle fasciculation and a decrease in indirect twitch tension in a chick biventer cervicis nerve-muscle bioassay. Interestingly, these effects were neutralised by antivenom raised against the venom of the Sydney funnel-web spider Atrax robustus. Subsequent whole-cell patch-clamp electrophysiology on rat dorsal root ganglion neurones revealed that δ-MSTX-Mb1a caused a reduction in peak tetrodotoxin (TTX)-sensitive sodium current, a slowing of sodium current inactivation and a hyperpolarising shift in the voltage at half-maximal activation. In addition, δ-MSTX-Mb1a failed to affect TTX-resistant sodium currents. Subsequent Edman degradation revealed a 42-residue peptide with unusual N- and C-terminal cysteines and a cysteine triplet (Cys14-16). This toxin was highly homologous to a family of δ-atracotoxins (δ-ACTX) from Australian funnel-web spiders including conservation of all eight cysteine residues. In addition to actions on sodium channel gating and kinetics to δ-ACTX, δ-MSTX-Mb1a caused significant insect toxicity at doses up to 2000 pmol/g. δ-MSTX-Mb1a therefore provides evidence of a highly conserved spider δ-toxin from a phylogenetically distinct spider family that has not undergone significant modification. © 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.	en_US
dc.relation	http://purl.org/au-research/grants/arc/DP0346325
dc.relation.ispartof	FEBS Letters	en_US
dc.relation.isbasedon	10.1016/S0014-5793(03)01175-X	en_US
dc.subject.classification	Biochemistry & Molecular Biology	en_US
dc.subject.mesh	Muscle, Skeletal	en_US
dc.subject.mesh	Peripheral Nerves	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Chickens	en_US
dc.subject.mesh	Spiders	en_US
dc.subject.mesh	Sodium Channels	en_US
dc.subject.mesh	Spider Venoms	en_US
dc.subject.mesh	Neurotoxins	en_US
dc.subject.mesh	Sequence Alignment	en_US
dc.subject.mesh	Sequence Analysis, Protein	en_US
dc.subject.mesh	Electrophysiology	en_US
dc.subject.mesh	Amino Acid Sequence	en_US
dc.subject.mesh	Molecular Sequence Data	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	In Vitro Techniques	en_US
dc.title	Isolation of δ-missulenatoxin-Mb1a, the major vertebrate-active spider δ-toxin from the venom of Missulena bradleyi (Actinopodidae)	en_US
dc.type	Journal Article
utslib.citation.volume	1-2	en_US
utslib.citation.volume	554	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	0304 Medicinal and Biomolecular Chemistry	en_US
utslib.for	0603 Evolutionary Biology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	1-2	en_US
pubs.publication-status	Published	en_US
pubs.volume	554	en_US

Abstract:

The present study describes the isolation and pharmacological characterisation of the neurotoxin δ-missulenatoxin-Mb1a (δ-MSTX-Mb1a) from the venom of the male Australian eastern mouse spider, Missulena bradleyi. This toxin was isolated using reverse-phase high-performance liquid chromatography and was subsequently shown to cause an increase in resting tension, muscle fasciculation and a decrease in indirect twitch tension in a chick biventer cervicis nerve-muscle bioassay. Interestingly, these effects were neutralised by antivenom raised against the venom of the Sydney funnel-web spider Atrax robustus. Subsequent whole-cell patch-clamp electrophysiology on rat dorsal root ganglion neurones revealed that δ-MSTX-Mb1a caused a reduction in peak tetrodotoxin (TTX)-sensitive sodium current, a slowing of sodium current inactivation and a hyperpolarising shift in the voltage at half-maximal activation. In addition, δ-MSTX-Mb1a failed to affect TTX-resistant sodium currents. Subsequent Edman degradation revealed a 42-residue peptide with unusual N- and C-terminal cysteines and a cysteine triplet (Cys14-16). This toxin was highly homologous to a family of δ-atracotoxins (δ-ACTX) from Australian funnel-web spiders including conservation of all eight cysteine residues. In addition to actions on sodium channel gating and kinetics to δ-ACTX, δ-MSTX-Mb1a caused significant insect toxicity at doses up to 2000 pmol/g. δ-MSTX-Mb1a therefore provides evidence of a highly conserved spider δ-toxin from a phylogenetically distinct spider family that has not undergone significant modification. © 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

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http://hdl.handle.net/10453/3837