Molecular docking study on the α3β2 neuronal nicotinic acetylcholine receptor complexed with α-Conotoxin GIC

• Published in: BMB reports Vol. 45; no. 5; pp. 275 - 280
• Main Authors: Lee, C.W., Biomedical Translational Research Center, KRIBB, Daejeon, Republic of Korea, Lee, S.H., Biomedical Translational Research Center, KRIBB, Daejeon, Republic of Korea, Kim, D.H., Biomedical Translational Research Center, KRIBB, Daejeon, Republic of Korea, Han, K.H., Biomedical Translational Research Center, KRIBB, Daejeon, Republic of Korea
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Biochemistry and Molecular Biology 01.05.2012; 생화학분자생물학회
• Subjects: alpha-Conotoxin GIC; Amino Acid Sequence; Animals; Conotoxins - chemistry; Conotoxins - metabolism; Conus Snail; Homology modeling; Ligand-docking; Models, Molecular; Molecular dynamics (MD) simulations; Molecular dynamics simulations; Molecular Sequence Data; Multiprotein Complexes - chemistry; NICOTINA; NICOTINE; Nicotinic acetylcholine receptors; Nicotinic acetylcholine receptors (nAChRs); Protein Binding - physiology; Protein Interaction Domains and Motifs - physiology; Protein Interaction Mapping - methods; Protein Structure, Quaternary; Protein Structure, Secondary; Receptors, Nicotinic - chemistry; Receptors, Nicotinic - metabolism; Substrate Specificity; α-Conotoxin GIC; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/BMBRep.2012.45.5.275

Nicotinic acetylcholine receptors (nAChRs) are a diverse family of homo- or heteropentameric ligand-gated ion channels. Understanding the physiological role of each nAChR subtype and the key residues responsible for normal and pathological states is important. α-Conotoxin neuropeptides are highly selective probes capable of discriminating different subtypes of nAChRs. In this study, we performed homology modeling to generate the neuronal α3, β2 and β4 subunits using the x-ray structure of the α1 subunit as a template. The structures of the extracellular domains containing ligand binding sites in the α3β2 and α3β4 nAChR subtypes were constructed using MD simulations and ligand docking processes in their free and ligand-bound states using α-conotoxin GIC, which exhibited the highest α3β2 vs. α3β4 discrimination ratio. The results provide a reasonable structural basis for such a discriminatory ability, supporting the idea that the present strategy can be used for future investigations on nAChR-ligand complexes.