Biophysical Approaches Facilitate Computational Drug Discovery for ATP-Binding Cassette Proteins

Figure 1

Architecture of prototypic human and bacterial ABC proteins. Human (P-gp/ABCB1, CFTR/ABCC7), rat (SUR1/ABCC8), and bacterial (Sav1866, MalEFGK₂, BtuC₂D₂F, and TM287/288) ABC proteins are shown relative to the plasma membrane [8–13]. P-gp is a multidrug transporter, CFTR is a unique chloride channel, SUR1 is a regulator of an inwardly rectifying potassium channel, Sav1866 is an exporter, MalEFGK₂ is a type I importer, BtuC₂D₂F is a type II importer, and TM287/288 is an exporter. MSDs are shown in green, NBDs are in orange, extracellular domains (ECMs) are in blue, R-domain is in pink, and the phospholipid bilayer is in gray. The core structure of an ABC protein consists of MSD1, NBD1, MSD2, and NBD2; however, SUR1/ABCC8 contains an additional MSD0. The full-length homology model of human CFTR is shown [14].