GTx1-15
GTx1-15 is a toxin from the Chilean tarantula venom that acts as both a voltage-gated calcium channel blocker and a voltage-gated sodium channel blocker.
Sources
[edit]GTx1-15 is derived from the Chilean tarantula species Grammostola rosea and Phrixotrichus scrofa.[1][2][3]
Chemistry
[edit]Sequence
[edit]GTx1-15 is composed of 34 amino acid residues; its sequence has been determined to be DCLGFMRKCIPDNDKCCRPNLVCSRTHKWCQYVF. This peptide has a molecular weight of approximately 4 kDa and is amidated at its carboxy terminus.[3]
Structure and Family
[edit]GTx1-15 belongs to the GTx1 family, which consists of long loop inhibitor cystine knot (ICK) motif toxins.[2] The GTx1-15 peptide has a conserved structure of six cysteine residues with the characteristic ICK motif,[1] which results in proteolytic, thermal, and chemical stability.[4]
Homology
[edit]GTx1-15 displays sequence homology with other ion channel toxins from several spider species. It is homologous in sequence with sodium channel blocker PaurTx3 by 76.5%, and it also shares similarities in sequence with HnTx-IV (60%), CcoTx2 (55.9%), TLTx1 (55.6%), ω-GrTx SIA (40%), GsAFII (38.2%) and GsMTx2 (38.2%).[1]
Target and Mode of Action
[edit]GTx1-15 targets low-voltage activated cation channels.[1] It specifically inhibits:
- T-type calcium channel Cav3.1[1]
- Sodium channels Nav1. GTx1-15 has a strong inhibitory effect on tetrodotoxin-sensitive (TTX-S) sodium channels (Nav1.7 and Nav1.3), but has a minimal effect on tetrodotoxin-resistant sodium channels (Nav1.5 and Nav1.8).[1][3]
The mode of action of GTx1-15 has not yet been clarified.[1]
IC50
[edit]The effectiveness of GTx1-15 as a blocker of human cloned Nav and Cav channels is summarized below:[3]
| Channels | IC50 |
|---|---|
| Cav3.1 | 0.01 μM |
| Nav1.7 | 0.007 μM |
| Nav1.3 | 0.12 ± 0.06 μM |
| Nav1.5 | No significant effect (up to 2 μΜ) |
| Nav1.8 | No significant effect (0.93 μM) |
References
[edit]- ^ a b c d e f g Ono S, Kimura T, Kubo T (September 2011). "Characterization of voltage-dependent calcium channel blocking peptides from the venom of the tarantula Grammostola rosea". Toxicon. 58 (3): 265–76. Bibcode:2011Txcn...58..265O. doi:10.1016/j.toxicon.2011.06.006. PMID 21740921.
- ^ a b Kimura T, Ono S, Kubo T (2012). "Molecular Cloning and Sequence Analysis of the cDNAs Encoding Toxin-Like Peptides from the Venom Glands of Tarantula Grammostola rosea". International Journal of Peptides. 2012: 731293. doi:10.1155/2012/731293. PMC 3303826. PMID 22500178.
- ^ a b c d Cherki RS, Kolb E, Langut Y, Tsveyer L, Bajayo N, Meir A (January 2014). "Two tarantula venom peptides as potent and differential Na(V) channels blockers". Toxicon. 77: 58–67. doi:10.1016/j.toxicon.2013.10.029. PMID 24211312.
- ^ Kikuchi K, Sugiura M, Kimura T (2015). "High Proteolytic Resistance of Spider-Derived Inhibitor Cystine Knots". International Journal of Peptides. 2015: 537508. doi:10.1155/2015/537508. PMC 4710912. PMID 26843868.