Diverse binding poses of agonistic neurotoxins on human Na_v1.6

Researchers published structures of three agonistic peptide toxins bound to the human Nav1.6–β1 channel complex on June 10, 2026, in Nature. These toxins, including bullet-ant-derived toxin δ-paraponeritoxin-Pc1a, cone snail ι-conotoxin RXIA, and the globular β-scorpion toxin Cn2, demonstrate diverse binding poses and mechanisms of action. The study reveals how these neurotoxins interact with the voltage-gated sodium channel Nav1.6, which is crucial for neuronal excitability. Understanding these distinct binding modes provides insights into the molecular basis of neurotoxin activity and could inform the development of new therapeutic strategies for neurological disorders associated with ion channel dysfunction. The specific structures elucidated offer a detailed atomic view of toxin-channel interactions, highlighting variations in how each toxin engages with the channel's pore or gating machinery. This work contributes to the broader field of structural biology and neuropharmacology by providing high-resolution data on critical protein-ligand interactions.