AA sequence: Tyr-Cys2-Gln-Lys-Trp-Leu-Trp-Thr-Cys9-Asp-Ser-Glu-Arg-Lys-Cys15-Cys16-Glu-Asp-Met-Val-Cys21-Arg-Leu-Trp-Cys25-Lys-Lys-Arg-Leu-NH2
Disulfide bonds: Cys2-Cys16, Cys9-Cys21, and Cys15-Cys25
Length (aa): 29
Formula: C160H245N47O41S7
Molecular Weight: 3707.48 Da
Appearance: White lyophilized solid
Solubility: aqueous buffer
CAS number: not available
Source: Synthetic
Purity rate: > 98%
GsAF-1
200 $ – 950 $
GsAF-1 blocks voltage-gated sodium channels
GsAF-1 (also termed β-theraphotoxin-Gr1b, GsAF-I) was originally isolated from the venom of Grammostola rosea spider. GsAF-I peptide toxin is reported to block the following voltage-gated sodium channel isoforms: Nav1.1, Nav1.2, Nav1.3, Nav1.4, Nav1.6 and Nav1.7 with respective IC50 values of 0.4, 0.6, 1.3, 0.3, 1.2 and 0.04 µM. In addition, the toxin blocks the hERG1 isoform with an IC50 value of 4.8 µM.
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Target Promiscuity and Heterogeneous Effects of Tarantula Venom Peptides Affecting Na+ and K+ Ion Channels
Venom-derived peptide modulators of ion channel gating are regarded as essential tools for understanding the molecular motions that occur during the opening and closing of ion channels. In this study, we present the characterization of five spider toxins on 12 human voltage-gated ion channels, following observations about the target promiscuity of some spider toxins and the ongoing revision of their “canonical” gating-modifying mode of action. The peptides were purified de novo from the venom of Grammostola rosea tarantulas, and their sequences were confirmed by Edman degradation and mass spectrometry analysis. Their effects on seven tetrodotoxin-sensitive Na+ channels, the three human ether-à-go-go (hERG)-related K+ channels, and two human Shaker-related K+ channels were extensively characterized by electrophysiological techniques. All the peptides inhibited ion conduction through all the Na+channels tested, although with distinctive patterns. The peptides also affected the three pharmaceutically relevant hERG isoforms differently. At higher concentrations, all peptides also modified the gating of the Na+ channels by shifting the activation to more positive potentials, whereas more complex effects were recorded on hERG channels. No effects were evident on the two Shaker-related K+ channels at concentrations well above the IC50 value for the affected channels. Given the sequence diversity of the tested peptides, we propose that tarantula toxins should be considered both as multimode and target-promiscuous ion channel modulators; both features should not be ignored when extracting mechanistic interpretations about ion channel gating. Our observations could also aid in future structure-function studies and might help the development of novel ion channel-specific drugs.
Elisa Redaelli, et al. (2010) Target Promiscuity and Heterogeneous Effects of Tarantula Venom Peptides Affecting Na+ and K+ Ion Channels. JBC. PMID: 19955179