Spider Toxin Card | ArachnoServer

Toxin Name	κ-theraphotoxin-Gr1a
Source Species	*Grammostola rosea* (Chilean rose tarantula)
Toxin Group	Theraphotoxin
Description	The toxin inhibits Kv2.1 and Kv4.2 voltage-gated potassium channels, but not Shaker-IR, Kv1.1, Kv1.3, Kv1.6, Kv2.1, Kv3.1 and eag channels. Inhibits also voltage-gated calcium channels (Cav2.1) with very low affinity compared to Kv channels. Inhibits rat Nav1.2 with similar affinity to Kv2.1. The toxin acts as a gating modifier by shifting channel openings to more depolarized voltages and multiple toxin molecules can simultaneously bind to a single channel. The toxin binding sites are situated in a α-helical region on the C-terminus of segment S3 of the channel (I273, F274, E277) and at least 20-25 Å away from the central pore. The toxin partitions into the membrane and interacts with the voltage sensor paddle. When the S3b-S4 paddle motifs of rat Nav1.2 are transplanted into Kv2.1, SGTx1 interacts with the domain I, domain II and domain IV chimeras, but not the domain III chimera.
Discovered	1995

Sex: female, Prosoma length: 26mm
Photo courtesy of Bastian Rast
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This toxin last updated on Feb 18, 2015

Taxonomy

Biological Activity

Accessions

Literature References

Original Deposition References
Swartz K.J., MacKinnon R. Neuron 15:941-949(1995). An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula.
Other References
Swartz K.J., MacKinnon R. Neuron 18:665-673(1997). Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites.
Swartz K.J., MacKinnon R. Neuron 18:675-682(1997). Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels.
Li-Smerin Y., Swartz K.J. Proc. Natl. Acad. Sci. U.S.A. 95:8585-8589(1998). Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels.
Garrett S.A., Mueller A.L., Sanguinetti M.C. Perspectives in Drug Discovery and Design 15/16:71-81(1999) Peptide toxins isolated from spider venom that modulate gating of voltage-dependent K+ channels
Takahashi H., Kim J.I., Min H.J., Sato K., Swartz K.J., Shimada I. J. Mol. Biol. 297:771-780(2000). Solution structure of hanatoxin1, a gating modifier of voltage- dependent K(+) channels: common surface features of gating modifier toxins.
Li-Smerin Y., Swartz K.J. J. Gen. Physiol. 115:673-684(2000). Localization and molecular determinants of the Hanatoxin receptors on the voltage-sensing domains of a K(+) channel.
Li-Smerin Y., Swartz K.J. J. Gen. Physiol. 117:205-218(2001). Helical structure of the COOH terminus of S3 and its contribution to the gating modifier toxin receptor in voltage-gated ion channels.
Shiau Y.S., Lin T.B., Liou H.H., Huang P.T., Lou K.L., Shiau Y.Y. Journal of molecular modeling 8:253-257(2002). Molecular simulation reveals structural determinants of the hanatoxin binding in Kv2.1 channels.
Lou K.L., Huang P.T., Shiau Y.S., Shiau Y.Y. J. Mol. Recognit. 15(4):175-179(2002) Molecular determinants of the hanatoxin binding in voltage-gated K+-channel drk1.
Huang P.T., Chen T.Y., Tseng L.J., Lou K.L., Liou H.H., Lin T.B., Spatz H.C., Shiau Y.Y. Recept. Channels 8:79-85(2002). Structural influence of hanatoxin binding on the carboxyl terminus of S3 segment in voltage-gated K(+)-channel Kv2.1.
Lou K.L., Huang P.T., Shiau Y.S., Liaw Y.C., Shiau Y.Y., Liou H.H. J. Mol. Recognit. 16(6):392-395(2003) A possible molecular mechanism of hanatoxin binding-modified gating in voltage-gated K+-channels.
Shiau Y.S., Huang P.T., Liou H.H., Liaw Y.C., Shiau Y.Y., Lou K.L. Chem. Res. Toxicol. 16:1217-1225(2003). Structural basis of binding and inhibition of novel tarantula toxins in mammalian voltage-dependent potassium channels.
Lee H.C., Wang J.M., Swartz K.J. Neuron 40:527-536(2003). Interaction between extracellular Hanatoxin and the resting conformation of the voltage-sensor paddle in Kv channels.
Phillips L.R., Milescu M., Li-Smerin Y., Mindell J.A., Kim J.I., Swartz K.J. Nature 436:857-860(2005). Voltage-sensor activation with a tarantula toxin as cargo.
Nishizawa M., Nishizawa K. Eur. Biophys. J. 35:373-381(2006). Interaction between K+ channel gate modifier hanatoxin and lipid bilayer membranes analyzed by molecular dynamics simulation.
Swartz K.J. Toxicon 49:213-230(2007). Tarantula toxins interacting with voltage sensors in potassium channels.
Milescu M., Vobecky J., Roh S.H., Kim S.H., Jung H.J., Kim J.I., Swartz K.J. J. Gen. Physiol. 130:497-511(2007). Tarantula toxins interact with voltage sensors within lipid membranes.
Huang P.T., Shiau Y.S., Lou K.L. Toxicon 49:285-292(2007). The interaction of spider gating modifier peptides with voltage-gated potassium channels.

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