title: Model of the extracellular domain of the human alpha7 nAChR based on the crystal structure of the mouse alpha1 nAChR extracellular domain.
abstract: 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 alpha1 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 alpha7 nAChR and investigated in detail the interface between the two alpha7 subunits. The docking of the agonist in the ligand-binding pocket of the human alpha7 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.
authors.affiliation: Department of Agricultural Biotechnology, Agricultural University of Athens, 75, Iera Odos, Votanikos, GR11855, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Konstantakaki
authors.forename: Socrates J
authors.initials: SJ
authors.lastname: Tzartos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Poulas
authors.forename: Elias
authors.initials: E
authors.lastname: Eliopoulos
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D015195:Drug Design; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011978:Receptors, Nicotinic / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
chemical_list: D008024:Ligands; D011978:Receptors, Nicotinic