Gating modifier toxins isolated from spider venom: Modulation of voltage-gated sodium channels and the role of lipid membranes.

ABSTRACT: Gating modifier toxins (GMTs) are venom-derived peptides isolated from spiders and other venomous creatures and modulate activity of disease-relevant voltage-gated ion channels and are therefore being pursued as therapeutic leads. The amphipathic surface profile of GMTs has prompted the proposal that some GMTs simultaneously bind to the cell membrane and voltage-gated ion channels in a trimolecular complex. Here, we examined whether there is a relationship among spider GMT amphipathicity, membrane binding, and potency or selectivity for voltage-gated sodium (Na_V) channels. We used NMR spectroscopy and in silico calculations to examine the structures and physicochemical properties of a panel of nine GMTs and deployed surface plasmon resonance to measure GMT affinity for li

SUBMITTER: Agwa AJ 

PROVIDER: S-EPMC5995520 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature