FIGURE 2.

Orthosteric and allosteric sites of the mAChRs. (A) Amino acid sequence alignment of the human M₁-M₅ mAChRs. The amino (N)-terminal tail, Intracellular loops (ICL), extracellular loops (ECL) and carboxy (C)-terminal tails are shown as black letters on a white background. Transmembrane domains (TMD) are shown as black letters on a gray background. Orthosteric site residues are white letters on a blue background. The intracellular loop three was truncated, as indicated by >< for presentation of the alignment. Alignment was performed using clustal omega. (B) X-ray crystal structure of the human M₄ mAChR (RCSB PDB number 5DSG), showing the location of orthosteric and allosteric sites. Orthosteric site residues are highlighted in blue, allosteric site residues are highlighted in black and residues that contribute to both binding pockets are highlighted in red.