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	Toxin Name ω-agatoxin-Aa3a Source Species Agelenopsis  aperta (Western grass spider) Toxin Group Agatoxin Description ω-AGTX-Aa3a is the prototypic member of a family of insecticidal and vertebrate-active toxins from Agelenopsis aperta that block a wide range of voltage-gated calcium (Cav) channels. The toxin blocks calcium channels in insect central neurons but not at peripheral neuromuscular junctions. In vertebrates, it is broadly activity against all high-threshold Cav1 channels and Cav2 channels, with radioligand binding studies indicating that the toxin defines a common high-affinity binding site (Kd = 5-10 pM) on vertebrate Cav2.1, 2.2 and 2.3 channels. However, the toxin is ineffective at blocking Cav3 (T-type) channels and it has no effect on voltage-dependent sodium and potassium currents in frog sympathetic or rat dorsal root ganglion neurons. Curiously, the toxin completely blocks L-type currents in myocardial cells but the block of Cav2 channels is only partial even at saturating concentrations of toxin. It has been suggested that the toxin occludes inward current by acting as a partial plug or "leaky lid" in the outer region of the channel vestibule. The binding sites for ω-AGTX-Aa3a and ω-AGTX-Aa4a on Cav2.1 (P/Q-type) channels are distinct and non-overlapping. [125I]-labelled toxin binds to neuron-rich layers in rat brain (such as the granule cell layer of the cerebellum and the pyramidal and granule cell layers of the hippocampal formation) and to areas rich in synaptic terminals (such as the substantia nigra reticulata and the molecular layers of the cerebellum and dentate gyrus of the hippocampal formation). Intracranial injection in mice leads to lethal convulsions. The toxin is present in A. aperta venom at low concentration (20 μM). Discovered 1991 This toxin last updated on Aug 20, 2010 Taxonomy Current Taxonomy Historic Taxonomy Kingdom Animalia Phylum Arthropoda Class Arachnida Order Araneae Infra-order Araneomorphae Family Agelenidae Genus Agelenopsis Species aperta Agelena aperta Agelenopsis aperta Agelenopsis aperta guttata Agelenopsis gertschi Biological Activity Neurotoxin Molecular Target ED50 IC50 Kd Pharmacophore Comment Calcium channel, voltage-gated (vertebrate): CaV2.2 1.4  nM Block of omega-conotoxin GIVA-sensitive Cav2.2 currents in frog sympathetic neurons Calcium channel, voltage-gated (invertebrate) 10.0  nM Block of Cav currents in locust thoracic ganglion neurons Calcium channel, voltage-gated (vertebrate): CaV1, non-specific 1.4  nM Block of dihydropyridine-sensitive L-type currents in rat dorsal root ganglion neurons Accessions Source Accession ArachnoServer AS000178 InterPro IPR005853 InterPro IPR013605 NCBI_Taxon 6908 Pfam PF08396 PIR A42335 PIR A54252 PROSITE PS60023 UniProt P33034 Literature References Original Deposition References Mintz I.M., Venema V.J., Adams M.E., Bean B.P. Proc. Natl. Acad. Sci. USA 88:6628-6631 (1991) Inhibition of N- and L-type Ca(2+) channels by the spider venom toxin omega-Aga-IIIA Venema V.J., Swiderek K.M., Lee T.D., Hathaway G.M., Adams M.E. J. Biol. Chem. 267:2610-2615 (1992) Antagonism of synaptosomal calcium channels by subtypes of omega-agatoxins. Other References Bindokas V.P., Venema V.J., Adams M.E. J. Neurophysiol. 66 :590-601 (1991) Differential antagonism of transmitter release by subtypes of omega-agatoxins Olivera B.M., Imperial J.S., Cruz L.J., Bindokas V.P., Venema V.J., Adams M.E. Ann. NY Acad. Sci. 635:114-122 (1991) Calcium channel-targeted polypeptide toxins Pocock J.M., Venema V.J., Adams M.E. Neurochem. Int. 20:263-70 (1992) Omega-agatoxins differentially block calcium channels in locust, chick and rat synaptosomes McIntosh J.M., Adams M.E., Olivera B.M., Filloux F. Brain Res. 594:109-114 (1992) Autoradiographic localization of the binding of calcium channel antagonist, [125I]omega-agatoxin IIIA, in rat brain Adams M.E., Myers R.A., Imperial J.S., Olivera B.M. Biochemistry 32:12566-12570 (1993) Toxityping rat brain calcium channels with omega-toxins from spider and cone snail venoms Ertel E.A., Warren V.A., Adams M.E., Griffin P.R., Cohen C.J., Smith M.M. Biochemistry 33:5098-5108 (1994) Type III omega-agatoxins: a family of probes for similar binding sites on L- and N-type calcium channels Olivera B.M., Miljanich G.P., Ramachandran J., Adams M.E. Annu. Rev. Biochem. 63:823-867 (1994) Calcium channel diversity and neurotransmitter release: the omega-conotoxins and omega-agatoxins Adams M.E., Olivera B.M. Trends Neurosci. 17:151-155 (1994) Neurotoxins: overview of an emerging research technology Yan L., Adams M.E. J. Biol. Chem. 275:21309-21316 (2000) The spider toxin omega-Aga IIIA defines a high affinity site on neuronal high voltage-activated calcium channels McDonough S.I., Boland L.M., Mintz I.M., Bean BP. J. Gen. Physiol. 119:313-328 (2002) Interactions among toxins that inhibit N-type and P-type calcium channels Protein Information Disulfide Bonds Left Residue Right Residue Evidence 2 19 Predicted 9 25 Predicted 16 52 Predicted 18 40 Predicted 27 38 Predicted 59 67 Predicted Sequences Peptide Sequences >as:ω-agatoxin-Aa3a|sp:P33034 Toxin (Omega-Aga-IIIA) from the venom of the spider Agelenopsis aperta that blocks Cav1 and Cav2 channels SCIDIGGDCDGEKDDCQCCRRNGYCSCYSLFGYLKSGCKCVVGTSAEFQGICRRKARQCY NSDPDKCESHNKPKRR Full BLAST BLAST mature toxin only Toxin Synonyms Synonym Type ω-agatoxin-Aa3a Recommended full name ω-AGTX-Aa3a Recommended abbreviation ω-agatoxin IIIA Synonym ω-Aga-IIIA Synonym (abbreviation)
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