Crystal structure of the monomeric extracellular domain of α9 nicotinic receptor subunit in complex with α-conotoxin RgIA: Molecular dynamics...
Zouridakis M., Papakyriakou A., Ivanov I. A., Kasheverov I. E., Tsetlin V., Tzartos S., Giastas P.
Frontiers in Pharmacology
Vol.10, IssueMAY, Num.474
Опубликовано: 2019
Тип ресурса: Статья
DOI:10.3389/fphar.2019.00474
Аннотация:
The α9 subunit of nicotinic acetylcholine receptors (nAChRs) exists mainly in heteropentameric assemblies with α10. Accumulating data indicate the presence of three different binding sites in α9α10 nAChRs: the α9(+)/α9(-), the α9(+)/α10(-), and the α10(+)/α9(-). The major role of the principal (+) side of the extracellular domain (ECD) of α9 subunit in binding of the antagonists methyllylcaconitine and α-bungarotoxin was shown previously by the crystal structures of the monomeric α9-ECD with these molecules. Here we present the 2.26-Å resolution crystal structure of α9-ECD in complex with α-conotoxin (α-Ctx) RgIA, a potential drug for chronic pain, the first structure reported for a complex between an nAChR domain and an α-Ctx. Superposition of this structure with those of other α-Ctxs bound to the homologous pentameric acetylcholine binding proteins revealed significant similarities in the orientation of bound conotoxins, despite the monomeric state of the α9-ECD. In addition, ligand-
Ключевые слова:
Molecular dynamics; Molecular modeling; Nicotinic acetylcholine receptors; RgIA; Structure; α-conotoxins
alpha conotoxin RgIA; conotoxin; nicotinic receptor; protein nicotinic receptor alpha10; protein nicotinic receptor alpha9; unclassified drug; Article; binding affinity; chronic pain; drug protein binding; drug structure; human; ligand binding; molecular dynamics; nonhuman; protein structure
Язык текста: Английский
ISSN: 1663-9812
Zouridakis M.
Papakyriakou A.
Ivanov I. A.
Kasheverov I. E. Igor` Evgenyevich 1966-
Tsetlin V.
Tzartos S.
Giastas P.
Зоуридакис М.
Папакyриакоу А.
Иванов И. А.
Кашеверов И. Е. Игорь Евгеньевич 1966-
Цетлин В.
Тзартос С.
Гиастас П.
Crystal structure of the monomeric extracellular domain of α9 nicotinic receptor subunit in complex with α-conotoxin RgIA: Molecular dynamics insights into RgIA binding to α9α10 nicotinic receptors
Crystal structure of the monomeric extracellular domain of α9 nicotinic receptor subunit in complex with α-conotoxin RgIA: Molecular dynamics...
Текст визуальный непосредственный
Frontiers in Pharmacology
Vol.10, IssueMAY Num.474
2019
Статья
Molecular dynamics Molecular modeling Nicotinic acetylcholine receptors RgIA Structure α-conotoxins
alpha conotoxin RgIA conotoxin nicotinic receptor protein nicotinic receptor alpha10 protein nicotinic receptor alpha9 unclassified drug Article binding affinity chronic pain drug protein binding drug structure human ligand binding molecular dynamics nonhuman protein structure
The α9 subunit of nicotinic acetylcholine receptors (nAChRs) exists mainly in heteropentameric assemblies with α10. Accumulating data indicate the presence of three different binding sites in α9α10 nAChRs: the α9(+)/α9(-), the α9(+)/α10(-), and the α10(+)/α9(-). The major role of the principal (+) side of the extracellular domain (ECD) of α9 subunit in binding of the antagonists methyllylcaconitine and α-bungarotoxin was shown previously by the crystal structures of the monomeric α9-ECD with these molecules. Here we present the 2.26-Å resolution crystal structure of α9-ECD in complex with α-conotoxin (α-Ctx) RgIA, a potential drug for chronic pain, the first structure reported for a complex between an nAChR domain and an α-Ctx. Superposition of this structure with those of other α-Ctxs bound to the homologous pentameric acetylcholine binding proteins revealed significant similarities in the orientation of bound conotoxins, despite the monomeric state of the α9-ECD. In addition, ligand-