Inhibition of Voltage-Gated Sodium Channels by Animal Toxins

TL;DR

This paper explores how animal toxins interact with voltage-gated sodium channels using advanced imaging and modeling techniques.

Contribution

The study introduces a novel methodology using CryoEM and deep-learning modeling to analyze toxin-channel interactions at high resolution.

Findings

CryoEM was used to study the structure of NaV1.8 in complex with Protoxin-I from a tarantula.

Comparative and deep-learning methods provided insights into cone snail toxin interactions with sodium channels.

The research reveals structural and functional details of toxin inhibition of sodium channels.

Abstract

Voltage-gated sodium channels (NaVs) play important roles in propagating action potentials and their structure and function can be modulated by a variety of factors, including animal toxins. Despite recent technological advances, channel and toxin structural studies still present many challenges. We used cryogenic electron microscopy (CryoEM) to study the tetrodotoxin-resistant human NaV 1.8 at high resolution and as a complex with a peptide derived from the Peruvian green velvet tarantula, Protoxin-I. We describe our methodology to bypass biochemical challenges and discuss the inhibition of the channel by the binding of Protoxin-I. We also gained information on a class of animal toxins derived from cone snails on a larger scale using both comparative and deep-learning modeling methods. These results give us a clearer picture of the interactions of animal toxins with NaVs.