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Computational determination of the binding mode of α-conotoxin to nicotinic acetylcholine receptor

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Abstract

Conotoxins belong to the large families of disulfide-rich peptide toxins from cone snail venom, and can act on a broad spectrum of ion channels and receptors. They are classified into different subtypes based on their targets. The α-conotoxins selectively inhibit the current of the nicotinic acetylcholine receptors. Because of their unique selectivity towards distinct nAChR subtypes, α-conotoxins become valuable tools in nAChR study. In addition to the X-ray structures of α-conotoxins in complex with acetylcholine-binding protein, a homolog of the nAChR ligand-binding domain, the high-resolution crystal structures of the extracellular domain of the α1 and α9 subunits are also obtained. Such structures not only revealed the details of the configuration of nAChR, but also provided higher sequence identity templates for modeling the binding modes of α-conotoxins to nAChR. This mini-review summarizes recent modeling studies for the determination of the binding modes of α-conotoxins to nAChR. As there are not crystal structures of the nAChR in complex with conotoxins, computational modeling in combination of mutagenesis data is expected to reveal the molecular recognition mechanisms that govern the interactions between α-conotoxins and nAChR at molecular level. An accurate determination of the binding modes of α-conotoxins on AChRs allows rational design of α-conotoxin analogues with improved potency or selectivity to nAChRs.

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  1. Key Laboratory of Marine Drugs of Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, P. R. China

    Nargis Tabassum, Rilei Yu & Tao Jiang

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  1. Nargis Tabassum
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  2. Rilei Yu
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Correspondence to Rilei Yu.

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Tabassum, N., Yu, R. & Jiang, T. Computational determination of the binding mode of α-conotoxin to nicotinic acetylcholine receptor. J. Ocean Univ. China 15, 1027–1033 (2016). https://doi.org/10.1007/s11802-016-3049-y

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  • DOI: https://doi.org/10.1007/s11802-016-3049-y

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