Natural Compounds Interacting with Nicotinic Acetylcholine Receptors: From Low-Molecular Weight Ones to Peptides and Proteins

Toxins

Denis Kudryavtsev²  Irina Shelukhina²  Catherine Vulfius⁴  Tatyana Makarieva³  Valentin Stonik³  Maxim Zhmak¹  Igor Ivanov²  Igor Kasheverov²  Yuri Utkin²  Victor Tsetlin² 

[1] SME Syneuro, Moscow 117997, Russia; E-Mail:;Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia; E-Mails:;Elyakov Pacific Institute of Bioorganic Chemistry, Far East Branch of the Russian Academy of Sciences, Vladivostok 690022, Russia; E-Mails:;Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino 142290, Russia; E-Mail:

关键词: α-conotoxins;    low-molecular weight agonists and antagonists;    α-neurotoxins;    nicotinic acetylcholine receptors;    snake venom phospholipases A2;    three-finger Ly6 proteins;   

DOI  :  10.3390/toxins7051683

来源: mdpi

【 摘 要 】

Nicotinic acetylcholine receptors (nAChRs) fulfill a variety of functions making identification and analysis of nAChR subtypes a challenging task. Traditional instruments for nAChR research are d-tubocurarine, snake venom protein α-bungarotoxin (α-Bgt), and α-conotoxins, neurotoxic peptides from Conus snails. Various new compounds of different structural classes also interacting with nAChRs have been recently identified. Among the low-molecular weight compounds are alkaloids pibocin, varacin and makaluvamines C and G. 6-Bromohypaphorine from the mollusk Hermissenda crassicornis does not bind to Torpedo nAChR but behaves as an agonist on human α7 nAChR. To get more selective α-conotoxins, computer modeling of their complexes with acetylcholine-binding proteins and distinct nAChRs was used. Several novel three-finger neurotoxins targeting nAChRs were described and α-Bgt inhibition of GABA-A receptors was discovered. Information on the mechanisms of nAChR interactions with the three-finger proteins of the Ly6 family was found. Snake venom phospholipases A₂ were recently found to inhibit different nAChR subtypes. Blocking of nAChRs in Lymnaea stagnalis neurons was shown for venom C-type lectin-like proteins, appearing to be the largest molecules capable to interact with the receptor. A huge nAChR molecule sensible to conformational rearrangements accommodates diverse binding sites recognizable by structurally very different compounds.

【 授权许可】

CC BY   
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