| First Author | Deuis JR | Year | 2021 |
| Journal | Front Pharmacol | Volume | 12 |
| Pages | 789570 | PubMed ID | 35095499 |
| Mgi Jnum | J:319734 | Mgi Id | MGI:6864907 |
| Doi | 10.3389/fphar.2021.789570 | Citation | Deuis JR, et al. (2021) The Tarantula Venom Peptide Eo1a Binds to the Domain II S3-S4 Extracellular Loop of Voltage-Gated Sodium Channel NaV1.8 to Enhance Activation. Front Pharmacol 12:789570 |
| abstractText | Venoms from cone snails and arachnids are a rich source of peptide modulators of voltage-gated sodium (NaV) channels, however relatively few venom-derived peptides with activity at the mammalian NaV1.8 subtype have been isolated. Here, we describe the discovery and functional characterisation of beta-theraphotoxin-Eo1a, a peptide from the venom of the Tanzanian black and olive baboon tarantula Encyocratella olivacea that modulates NaV1.8. Eo1a is a 37-residue peptide that increases NaV1.8 peak current (EC50 894 +/- 146 nM) and causes a large hyperpolarising shift in both the voltage-dependence of activation (DeltaV50-20.5 +/- 1.2 mV) and steady-state fast inactivation (DeltaV50-15.5 +/- 1.8 mV). At a concentration of 10 muM, Eo1a has varying effects on the peak current and channel gating of NaV1.1-NaV1.7, although its activity is most pronounced at NaV1.8. Investigations into the binding site of Eo1a using NaV1.7/NaV1.8 chimeras revealed a critical contribution of the DII S3-S4 extracellular loop of NaV1.8 to toxin activity. Results from this work may form the basis for future studies that lead to the rational design of spider venom-derived peptides with improved potency and selectivity at NaV1.8. |
