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

Journal: Science

Published: 2018-10-19

DOI: 10.1126/science.aau2596

Affiliations: 8

Authors: 12

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Research Highlight

Structure of cockroach protein could lead to new painkillers

© PetePattavina/Getty

© PetePattavina/Getty

A detailed blueprint of how an ion channel interacts with neurotoxins at the molecular level could help guide the development of drugs for diseases caused by the aberrant transmission of electrical signals in muscles and neurons.

A Chinese–Australian team that included University of Queensland researchers used cryo-electron microscopy to create a high-resolution map of the voltage-gated sodium channel protein from cockroaches in complex with neurotoxins produced by three venomous animals — spiders, pufferfish and shellfish. Two of these toxins block the ion channel, while the other traps the channel in a particular conformation.

The structural insights gleaned from how the different toxins bind will be considerations as drug companies aim to target voltage-gated sodium channels for treating epilepsy, arrhythmia, pain and other conditions caused by defects in these channels.

Supported content

  1. Science 362, eaau2596 (2018). doi: 10.1126/science.aau2596
Institutions FC
Institute for Molecular Bioscience (IMB), UQ, Australia 0.42
State Key Laboratory of Membrane Biology (LMB), Tsinghua, China 0.10
School of Life Sciences, Tsinghua, China 0.10
School of Medicine, Tsinghua, China 0.10
Beijing Advanced Innovation Center for Structural Biology (ICSB-BJ), China 0.10
Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program (PTN), China 0.10
Technology Center for Protein Sciences, Tsinghua, China 0.04
MOE Key Laboratory of Protein Sciences, Tsinghua, China 0.04

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