Structure, orientation, and conformational changes in transmembrane domains of multidrug transporters.
Multidrug transporter proteins promote the active transmembrane efflux of noxious drugs, thereby decreasing their accumulation in the intracellular medium and reducing their therapeutic efficiency. Expression of such proteins drastically reduces the efficiency of chemotherapeutic treatments against cancer and various infectious diseases. To overcome major difficulties related to the crystallization of membrane proteins, other experimental approaches have been developed to gain information on the structural changes involved in drug transport. We examine here and illustrate with a few examples how infrared and fluorescence spectroscopy can provide new insights into the structure of the membrane domains of multidrug transporters in particular. Such domains contain the drug-binding site(s) and mediate the passage of substrates across the cell membrane.
Vigano
Catherine
C
Laboratory for Structure and Function of Biological Membranes, Structural Biology and Bioinformatics Center, Free University of Brussels, Brussels, Belgium.
Manciu
Liliana
L
Ruysschaert
Jean-Marie
JM
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000502:physiology; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013499:Surface Properties
D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1