Figure 1.

Alternating access model of Pgp with large NBD–NBD separation in the apo-state. Binding of ATP to the NBDs promotes the transition from the nucleotide-free inward-facing conformation (apo; PDB code 4Q9H) to the outward-facing conformation (nucleotide-bound model (46) based on the X-ray crystal structure of nucleotide-bound Sav1866; PDB code 2ONG). The first and second homologous halves are represented in gray and blue, respectively. In this study, Asn-607 and Thr-1252 (red spheres) were mutated to Cys to chemically attach LRET probes. The approximate position of the membrane is between the lines on the right. TMD, transmembrane domain; NBDs, nucleotide-binding domains.