CSTX (for "'' Cupiennius salei'' toxins") is a name given to a group of closely related

neurotoxic Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...

peptides present in the venom of the

wandering spider Wandering spiders (''Ctenidae'') are a family (biology), family of spiders that includes the Phoneutria, Brazilian wandering spiders. These spiders have a distinctive longitudinal groove on the top-rear of their oval carapace similar to those of t ...

''Cupiennius salei''. There are twenty types so far described for this protein group. However, some are reclassified into cupiennins group of toxin, including CSTX-3, -4, -5, and -6, because of their chemical affinity. The first thirteen were isolated and identified in 1994 by Lucia Kuhn-Nentwig, Johann Schaller, and Wolfgang Nentwig of the Zoological Institute at the

University of Bern The University of Bern (german: Universität Bern, french: Université de Berne, la, Universitas Bernensis) is a university in the Switzerland, Swiss capital of Bern and was founded in 1834. It is regulated and financed by the Canton of Bern. It ...

Switzerland ). Swiss law does not designate a ''capital'' as such, but the federal parliament and government are installed in Bern, while other federal institutions, such as the federal courts, are in other cities (Bellinzona, Lausanne, Luzern, Neuchâtel ...

. The different types are most likely the products of splicing variant of the same gene. They are all L-type

calcium channel blockers Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

, and also exhibit cytolytic activity by forming an alpha-helix across the

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

in mammalian

neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

. They also inhibit

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, etc.) with a permeabili ...

in insect neurons.

Types

The best understood members of the neurotoxin group of CSTX are:

CSTX-1

CSTX-1 is the most abundant peptide of the venom of ''C. salei'' with concentration ranging from 1.4 to 3.3 mM. It is the most toxic component, and is the principle neurotoxin of the spider. It is highly basic containing four

disulfide bridges In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...

, which form 'disulfide through disulfide knot', thus, structurally defines this protein as a knottin. It has two natural degradation products, namely CSTX-2a and CSTX-2b, which occur in low amount and are less toxic than the CSTX-1 itself. CSTX-2a is composed of 61 amino acid residues and has a mass of 6864 Da, while CSTX-2b is made up of 60 amino acids having a size of 6708 Da. CSTX-2a is a variation of the same gene product, and it differs from CSTX-1 only on the last 13 amino acids of the C-terminal. The 13-amino acid terminal is unusually rich in lysine (7 in number) are attributed to the higher toxicity of CSTX-1. This makes CSTX-2a seven times less toxic than CSTX-1. Further, CSTX-2b also lacks arginine at position 61 compared to CSTX-1, and this reduces the

neurotoxicity Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...

by 190-fold. CSTX-1 exerts two different functions: as a neurotoxin it inhibits L-type calcium channels, and as a cytolytic peptide it destroys the cell membrane.

References

External links

Information at UniProt
{{Toxins Toxins Neurotoxins Ion channel toxins Spider toxins