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Heteroscodratoxin-1
Names
	Other names kappa-theraphototoxin Hm1a, HmTx1
Identifiers
Properties
Chemical formula	C170H245N47O54S6
Molar mass	4003.47 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

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Heteroscodratoxin-1 (also known as kappa-theraphototoxin Hm1a or HmTx1) is a neurotoxin produced by the venom glands of the Heteroscodra maculata (Togo starburst tarantula) Cite error: The <ref> tag has too many names (see the help page). that shifts the activation threshold of voltage-gated potassium channels to more positive potentials. ^[1]

Source

Heteroscodratoxin-1 can be obtained from venom glands of the Heteroscodra maculata (Togo starburst tarantula or Togo starburst baboon spider). ^[1]

Chemistry

Heteroscodratoxin-1 is a basic protein (isoelectric point of 7.69) composed of 35 amino acids with a carboxylated C-terminus. Its sequence shows strong similarity with other taruntala toxins such as Scodratoxin, Hanatoxin and SGTx1. Structurally the protein belongs to the huwentoxin-1 family of inhibitory spider peptides based on its knottin backbone that consists of three crossing disulfide bridges (Cys1-Cys4/Cys2-Cys5/Cys3-Cys6). ^[1]

Target

Heteroscodratoxin-1 inhibits subtypes of both delayed rectifier (K_V2.1/ KCNB1 and K_V2.2/ KCNB2) and A type rapidly inactivating (K_V4.1/ KCND1, K_V4.2/ KCND2 and K_V4.3/ KCND3) voltage-gated potassium channels. The amount of conductance depression evoked at 0 mV has been determined in COS cells:

23% on K_V2.1 at 100 nM
19% on K_V2.2 at 100 nM
50% on K_V4.1 at 280 nM
39% on K_V4.2 at 300 nM
43% on K_V4.3 at 300 nM.

Conversely under the same experimental conditions no significant effect (defined as less than 20% inhibition at 300 nM) has been found on the currents through other A type rapidly inactivating (K_V1.4 and K_V3.4) or delayed rectifier potassium channels (K_V1.1, K_V1.2, K_V1.3, K_V1.5, K_V1.6, K_V1.2/ K_V1.5, or K_VLQT1). Sodium and calcium channels also seem unaffected as perfusion of rat granular cells with 100 nM heteroscodratoxin-1 does not change ion flow (less than 5% inhibition) accross the membrane at 0 mV. ^[1]

Mode of action

It is thought that heteroscodratoxin-1 modifies gating of specific potassium channels by shifting the activation threshold to more positive values resulting in a decrease of current amplitude at a given potential. The mechanism underlying this modification has been largely elucidated using molecular docking simulation for the K_V2.1 potassium channel which is highly expressed in mammalian neurons and interacts strongly with heteroscodratoxin-1. In this model the C-terminal residue of the K_V2.1 S3-segment (S3_C) serves as a binding site for Hmtx-1 forming both hydrophobic and hydrophilic bonds (van der Waals strength of 402.27 kcal/mol). Interaction between the toxin and the potassium channel induces a helical movement of S3_C resulting in limited spatial freedom of the S4-segment which is responsible for channel gating. ^[2]

Toxicity

Information on toxic effects of Heteroscodratoxin-1 in humans is not available. In mice however it has been found that intracerebroventricular injection of 500 pmol HmTx1 induces convulsions, spasms, tremors and death within 1 hour. At 100 pmol a less severe response develops though death still occurs after 2 hours. ^[1]

References

"Kappa-theraphotoxin-Hm1a - Heteroscodra maculata (Togo starburst tarantula)". Uniprot.org. 2011-09-21. Retrieved 2011-10-08.
Escoubas, Pierre (2002). "Novel tarantula toxins for subtypes of voltage-dependent potassium channels in the Kv2 and Kv4 subfamilies". Molecular Pharmacology. 62 (1): 48–57. doi:10.1124/mol.62.1.48. PMID 12065754.
Shiau, Yu-Shuan (2003). "Structural Basis of Binding and Inhibition of Novel Tarantula Toxins in Mammalian Voltage-Dependent Potassium Channels". Chemical Research in Toxicology. 16 (10): 1217–1225. doi:10.1021/tx0341097. PMID 14565763.

External links

Heteroscodratoxin-1 from the Uniprot website
Toxin card for Heteroscodratoxin-1 from the Toxin, Toxin-target database website

Category:Ion channel toxins Category: Neurotoxins Category:Invertebrate toxins

[Escoubas2002-1] Escoubas 2002

[Shiau2003-2] Shiau 2003

[1]

[2]