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

Abstract:

: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.

journal_name

BMB Rep

journal_title

BMB reports

authors

Lee C,Lee SH,Kim DH,Han KH

doi

10.5483/bmbrep.2012.45.5.275

subject

Has Abstract

pub_date

2012-05-01 00:00:00

pages

275-80

issue

5

eissn

1976-6696

issn

1976-670X

journal_volume

45

pub_type

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