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Snake α-Neurotoxins and the Nicotinic Acetylcholine Receptor

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Snake Venoms

Part of the book series: Toxinology ((TOXI))

Abstract

α-Neurotoxins from snake venoms act on postsynaptic nicotinic acetylcholine receptors at the neuromuscular junction to produce clinically significant skeletal muscle paralysis following envenomation. From the seminal discovery almost 50 years ago of α-bungarotoxin, the prototypical α-neurotoxin, our knowledge of the composition of snake venoms, snake envenomation and its treatment, physiology of the neuromuscular junction, structure and function of nicotinic acetylcholine receptors, protein-protein interactions, and pathophysiological mechanisms that underpin diseases like myasthenia gravis has grown exponentially. The potential for the discovery of therapeutic lead compounds from snake venoms has also been advanced. This review looks back at the historical milestones of this research; highlights the challenges of nomenclature pertaining to the increasing number of novel toxins; provides an overview of nicotinic acetylcholine receptors and their subtypes; discusses the classification of snake α-neurotoxins; describes the three-finger protein fold that is the characteristic scaffold of most snake α-neurotoxins, while noting the unique exceptions; details the pharmacology of snake α-neurotoxins including their mechanisms of neuromuscular blockade, reversibility of blockade, and differential binding affinities for the two different acetylcholine-binding sites on the muscle nicotinic receptor; and lastly, delivers an updated and in-depth analysis of the structure-function relationships of the α-neurotoxin–nicotinic acetylcholine receptor interaction, including information gleaned from mutational, computer modeling, and structural studies of complexes formed between α-neurotoxins and receptor components or homologues. These new facets in toxinology have significantly broadened the scope of α-neurotoxins in scientific discovery as well as their therapeutic potential.

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Authors and Affiliations

  1. School of Medicine, Griffith University, Gold Coast, QLD, Australia

    Selvanayagam Nirthanan

  2. School of Medical Science, Griffith University, Gold Coast, QLD, Australia

    Selvanayagam Nirthanan & Wasim Awal

  3. Menzies Health Institute Queensland, Gold Coast, QLD, Australia

    Selvanayagam Nirthanan

  4. Faculty of Science, University of Queensland, Brisbane, QLD, Australia

    Navin R. Niranjan

Authors
  1. Selvanayagam Nirthanan
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  2. Wasim Awal
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  3. Navin R. Niranjan
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Correspondence to Selvanayagam Nirthanan , Wasim Awal or Navin R. Niranjan .

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Editors and Affiliations

  1. Biomedical Research Institute National Institute of Advanced Industria, Tsukuba, Ibaraki, Japan

    Hidetoshi Inagaki

  2. University of Hawaii Cancer Center, Honolulu, Hawaii, USA

    Carl-Wilhelm Vogel

  3. Department of Molecular Biology and Biot, Tezpur University, Tezpur, Assam, India

    Ashis K. Mukherjee

  4. Egyptian Society of Natural Toxins and Z, Faculty of Science Suez Canal University, Ismailia, Egypt

    Tarek R. Rahmy

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Nirthanan, S., Awal, W., Niranjan, N.R. (2017). Snake α-Neurotoxins and the Nicotinic Acetylcholine Receptor. In: Inagaki, H., Vogel, CW., Mukherjee, A., Rahmy, T. (eds) Snake Venoms. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6410-1_29

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