Blockade of Neuronal α7-nAChR by α-Conotoxin ImI Explained by Computational Scanning and Energy Calculations
Figure 2
Sequence and structure of α7-nAChR ligand-binding domain.
Sequence alignment of Homo sapiens α7-nAChR ligand-binding domain (LBD) (UniProtKB/SwissProt P36544), Mus musculus α1-nAChR LBD (PDB ID: 1pq1), and Aplysia californica AChBP (PDB ID: 1tg9), which is structurally analogous to nAChRs. Below the alignment, the secondary structure elements and acetylcholine binding sites are shown on the lowest energy three-dimensional model of the α7-nAChR nAChR LBD obtained by comparative modeling. Residues in the sequence alignment are numbered according to the α7-nAChR sequence. The conserved positions between the three sequences are on a dark green background, whereas the positions presenting amino acids shared by only two sequences are on a light green background. The secondary structure elements are the α-helix h1 and the β-strands β1-10. The LBD is a pentamer of five subunits. The acetylcholine binding sites, indicated by star symbols, are located at the interface between the subunits. These binding sites mainly comprise the C-loop from one subunit, which is designated as the principal subunit, and the beta strands β1, β2, β3, β5′ and β6 from another subunit, which is designated as the complementary subunit. The secondary structures of one subunit are highlighted in the side view, and the arrangement of the subunits and of the binding sites is shown on the top view. In the alignment, the residues of AChBP in contact with ImI in the crystal structure 2c9t are underlined in blue for positions in the principal subunit and in white for positions in the complementary subunit.