Model of the extracellular domain of the human alpha 7 nAChR based on the crystal structure of the mouse alpha 1 nAChR extracellular domain

Neuronal nicotinic acetylcholine receptors (nAChRs) are important therapeutic targets for various diseases, including Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for cessation of smoking. Based on the recently determined crystal structure of the extracellular do...

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Bibliographic Details
Published in:Journal of molecular graphics & modelling 2008-06, Vol.26 (8), p.1333-1337
Main Authors: Konstantakaki, M, Tzartos, S J, Poulas, K, Eliopoulos, E
Format: Article
Language:English
Online Access:Get full text
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Summary:Neuronal nicotinic acetylcholine receptors (nAChRs) are important therapeutic targets for various diseases, including Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for cessation of smoking. Based on the recently determined crystal structure of the extracellular domain (ECD) of the mouse nAChR alpha 1 subunit complexed with alpha -bungarotoxin at 1.94A resolution, we have constructed three-dimensional models of the ECD of the monomer, homodimer, and homopentamer of the human alpha 7 nAChR and investigated in detail the interface between the two alpha 7 subunits. The docking of the agonist in the ligand-binding pocket of the human alpha 7 dimer was also performed and found consistent with results from labeling and mutagenesis experiments. Since the nAChR ligand-binding site is a useful target for mutagenesis studies and the rational design of drugs against diseases, these models provide useful information for future work.
ISSN:1093-3263
DOI:10.1016/j.jmgm.2008.01.004