CSTX
CSTX (for "Cupiennius salei toxins") is a name given to a group of closely related neurotoxic peptides present in the venom of the wandering spider 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, Switzerland.[1] The different types are most likely the products of splicing variant of the same gene. They are all L-type calcium channel blockers, and also exhibit cytolytic activity by forming an alpha-helix across the cell membrane in mammalian neurons. They also inhibit voltage-gated calcium channels in insect neurons.[2]
Types
[edit]The best understood members of the neurotoxin group of CSTX are:
| Name | Recommended name | Size in Da | Amino acid residue | Toxicity (LD50) on Drosophilla |
|---|---|---|---|---|
| CSTX-1 | Omega-ctenitoxin-Cs1a | 8,352 | 74 | 0.35 pmol/mg |
| CSTX-8 | Toxin CSTX-8 | 7,378 | 63 | |
| CSTX-9 | U1-ctenitoxin-Cs1a | 7,529 | 68 | 10.6 pmol/mg |
| CSTX-10 | Toxin CSTX-10 | 8,110 | 69 | |
| CSTX-11 | Toxin CSTX-11 | 8,083 | 69 | |
| CSTX-12 | Toxin CSTX-12 | 7,312 | 63 | |
| CSTX-13 | U2-ctenitoxin-Cs1a | 7,359 | 63 | 16.3 nmol/g |
| CSTX-14 | Toxin CSTX-14 | 5,657 | 48 | |
| CSTX-15 | Toxin CSTX-15 | 5,612 | 48 | |
| CSTX-16 | Toxin CSTX-16 | 4,748 | 38 | |
| CSTX-17 | Toxin CSTX-17 | 4,410 | 14 | |
| CSTX-18 | Toxin CSTX-18 | 5,611 | 51 | |
| CSTX-19 | Toxin CSTX-19 | 3,748 | 35 | |
| CSTX-20 | Toxin CSTX-20 | 9,918 | 86 |
CSTX-1
[edit]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, 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 by 190-fold.[3] 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.[4]
References
[edit]- ^ Kuhn-Nentwig L, Schaller J, Nentwig W (1994). "Purification of toxic peptides and the amino acid sequence of CSTX-1 from the multicomponent venom of Cupiennius salei (Araneae:Ctenidae)". Toxicon. 32 (3): 287–302. doi:10.1016/0041-0101(94)90082-5. PMID 8016851.
- ^ Kuhn-Nentwig L, Schaller J, Nentwig W (2004). "Biochemistry, toxicology and ecology of the venom of the spider Cupiennius salei (Ctenidae)". Toxicon. 43 (5): 543–553. doi:10.1016/j.toxicon.2004.02.009. PMID 15066412.
- ^ Kuhn-Nentwig L, Schaller J, Kämpfer U, Imboden H, Malli H, Nentwig W (2000). "A lysine rich C-terminal tail is directly involved in the toxicity of CSTX-1, a neurotoxic peptide from the venom of the spider Cupiennius salei". Archives of Insect Biochemistry and Physiology. 44 (3): 101–111. doi:10.1002/1520-6327(200007)44:3<101::AID-ARCH1>3.0.CO;2-S. PMID 10897091.
- ^ Kuhn-Nentwig L, Fedorova IM, Lüscher BP, Kopp LS, Trachsel C, Schaller J, Vu XL, Seebeck T, Streitberger K, Nentwig W, Sigel E, Magazanik LG (2012). "A venom-derived neurotoxin, CsTx-1, from the spider Cupiennius salei exhibits cytolytic activities". J Biol Chem. 287 (30): 25640–25649. doi:10.1074/jbc.M112.339051. PMC 3408166. PMID 22613721.
