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.
Chemistry
Sequence
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.Structure and Family
GTx1-15 belongs to the GTx1 family, which consists of long loop inhibitor cystine knot motif toxins. The GTx1-15 peptide has a conserved structure of six cysteine residues with the characteristic ICK motif, which results in proteolytic, thermal, and chemical stability.Homology
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, CcoTx2, TLTx1, ω-GrTx SIA, GsAFII and GsMTx2.Target and Mode of Action
GTx1-15 targets low-voltage activated cation channels. It specifically inhibits:- T-type calcium channel Cav3.1
- Sodium channels Nav1. GTx1-15 has a strong inhibitory effect on tetrodotoxin-sensitive sodium channels, but has a minimal effect on tetrodotoxin-resistant sodium channels.
IC50
The effectiveness of GTx1-15 as a blocker of human cloned Nav and Cav channels is summarized below:| Channels | IC50 |
| Cav3.1 | 0.01 μM |
| Nav1.7 | 0.007 μM |
| Nav1.3 | 0.12 ± 0.06 μM |
| Nav1.5 | No significant effect |
| Nav1.8 | No significant effect |