Cross-linking, DEER-spectroscopy and molecular dynamics confirm the inward facing state of P-glycoprotein in a lipid membrane

The drug efflux pump P-glycoprotein (P-gp) displays a complex transport mechanism involving multiple drug binding sites and two centres for nucleotide hydrolysis. Elucidating the molecular mechanism of transport remains elusive and the availability of P-gp structures in distinct natural and ligand trapped conformations will accelerate our understanding. The present investigation sought to provide biochemical data to validate specific features of...