Grammotoxin

Grammotoxin is a toxin in the venom of the tarantula Grammostola spatulata. It is a protein toxin that inhibits P-, Q- and N-type voltage-gated calcium channels (Ca ²⁺ channels) in neurons. Grammotoxin is also known as omega-grammotoxin SIA.

Solution structure of omega-grammotoxin SIA. PDB entry 1koz^[1]

Chemistry

Grammotoxin is a 36 amino acid protein toxin, with the sequence Asp-Cys-Val-Arg-Phe-Trp-Gly-Lys-Cys-Ser-Gln-Thr-Ser-Asp-Cys-Cys-Pro-His-Leu-Ala-Cys-Lys-Ser-Lys-Trp-Pro-Arg-Asn-Ile-Cys-Val-Trp-Asp-Gly-Ser-Val (DCVRFWGKCSQTSDCCPHLACKSKWPRNICVWDGSV), and disulfide bridges between Cys2-Cys16, Cys9-Cys21 and Cys15-Cys30.

It forms an inhibitor cystine knot motif, common in spider toxins.^[1]

Its chemical formula is: C₁₇₇H₂₆₈N₅₂O₅₀S₆^[2]

Grammotoxin can be purified from Grammostola spatulata venom by reverse phase high performance liquid chromatography.^[3]

Mode of action

The toxin binding site on the channels has high affinity for the toxins when they are closed and low affinity when channels are activated.^[4] As a result, the toxin preferentially binds to the closed channels. It binds at a region which contains the voltage-sensing domains. When bound, the toxin makes it more difficult for channels to be opened by depolarization, so much larger depolarizations are required for channel activation.^[4] Grammotoxin also binds to potassium channels but with lower affinity than to the calcium channels.^[1]