Structural basis for the modulation of voltage-gated sodium channels by animal toxins

• DOI: 10.1126/science.aau2596
• Publication Date: 2018-07-26T18:06:54Z
• Authors: Huaizong Shen; Zhangqiang Li; Yan Jiang; Xiaojing Pan; Jianping Wu; Ben Cristofori-Ar...; Jennifer J. Smith; Yanni K. Y. Chin; Jianlin Lei; Qiang Zhou; Glenn F. King; Nieng Yan
• Keywords: Voltage-Gated Sodium Channel Blockers; 0301 basic medicine; Multidisciplinary; Cryoelectron Microscopy; Spider Venoms; Tetrodotoxin; Voltage-Gated Sodium Channels; 3. Good health; 03 medical and health sciences; Protein Domains; 1000 General; Animals; Insect Proteins; Periplaneta; Amino Acid Sequence; Ion Channel Gating; Saxitoxin

Structures of voltage-gated sodium channels

In “excitable” cells, like neurons and muscle cells, a difference in electrical potential is used to transmit signals across the cell membrane. This difference is regulated by opening or closing ion channels in the cell membrane. For example, mutations in human voltage-gated sodium (Na v ) channels are associated with disorders such as chronic pain, epilepsy, and cardiac arrhythmia. Pan et al. report the high-resolution structure of a human Na v channel, and Shen et al. report the structures of an insect Na v channel bound to the toxins that cause pufferfish and shellfish poisoning in humans. Together, the structures give insight into the molecular basis of sodium ion permeation and provide a path toward structure-based drug discovery.

Science , this issue p. eaau2486 , p. eaau2596