Grammotoxin is a

toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

in the

venom Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a sti ...

of the

tarantula Tarantulas comprise a group of large and often hairy spiders of the family Theraphosidae. , 1,100 species have been identified, with 166 genera. The term "tarantula" is usually used to describe members of the family Theraphosidae, although ...

'' Grammostola spatulata''. It is a protein toxin that inhibits P-, Q- and N-type

voltage-gated calcium channels Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'' muscle, glial cells, neurons) with a permeability to ...

(Ca ²⁺ channels) in

neurons A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

. Grammotoxin is also known as omega-grammotoxin SIA.

Chemistry

Grammotoxin is a 36

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

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 An inhibitor cystine knot (also known as ICK or Knottin) is a protein structural motif containing three disulfide bridges. Knottins are one of three folds in the cystine knot motif; the other closely related knots are the growth factor cystine kn ...

motif, common in spider toxins. Its chemical formula is: C₁₇₇H₂₆₈N₅₂O₅₀S₆ Grammotoxin can be purified from ''Grammostola spatulata'' venom by reverse phase

high performance liquid chromatography High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify specific components in mixtures. The mixtures can origina ...

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. 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

makes it more difficult for channels to be opened by

depolarization In biology, depolarization or hypopolarization is a change within a cell (biology), cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolar ...

, so much larger

s are required for channel activation. Grammotoxin also binds to

potassium channels Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of ...

but with lower affinity than to the

calcium channels A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, which are a type of calcium channel regulated by changes in membrane potential. Some calcium chan ...

References

{{reflist Neurotoxins Ion channel toxins