title: Natural compounds interacting with nicotinic acetylcholine receptors: from low-molecular weight ones to peptides and proteins.
abstract: 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.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia. kudryavtsev@ibch.ru.
authors.forename: Denis
authors.initials: D
authors.lastname: Kudryavtsev
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia. ner-neri@mail.ru.
authors.forename: Irina
authors.initials: I
authors.lastname: Shelukhina
authors.affiliation: Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino 142290, Russia. vulfius@gmail.com.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vulfius
authors.affiliation: Elyakov Pacific Institute of Bioorganic Chemistry, Far East Branch of the Russian Academy of Sciences, Vladivostok 690022, Russia. makarieva@piboc.dvo.ru.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Makarieva
authors.affiliation: Elyakov Pacific Institute of Bioorganic Chemistry, Far East Branch of the Russian Academy of Sciences, Vladivostok 690022, Russia. stonik@piboc.dvo.ru.
authors.forename: Valentin
authors.initials: V
authors.lastname: Stonik
authors.affiliation: SME Syneuro, Moscow 117997, Russia. mzhmak@gmail.com.
authors.forename: Maxim
authors.initials: M
authors.lastname: Zhmak
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia. chai.mail0@gmail.com.
authors.forename: Igor
authors.initials: I
authors.lastname: Ivanov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia. iekash@mx.ibch.ru.
authors.forename: Igor
authors.initials: I
authors.lastname: Kasheverov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia. utkin@mx.ibch.ru.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Utkin
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia. vits@ibch.ru.
authors.forename: Victor
authors.initials: V
authors.lastname: Tsetlin
mesh_terms: D000818:Animals; D020916:Conotoxins / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008970:Molecular Weight; D018722:Nicotinic Agonists / Q000737:chemistry / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D020916:Conotoxins; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D010455:Peptides; D011506:Proteins; D011978:Receptors, Nicotinic
keywords: low-molecular weight agonists and antagonists; nicotinic acetylcholine receptors; snake venom phospholipases A2; three-finger Ly6 proteins; α-conotoxins; α-neurotoxins