Exploring the structure and function of the P-glycoprotein multidrug transporter using fluorescence spectroscopic tools

• Published in: Seminars in cell & developmental biology 2001-06, Vol.12 (3), p.257-265
• Main Authors: Sharom, Frances J., Liu, Ronghua, Qu, Qin, Romsicki, Yolanda
• Format: Article
• Language: English
• Subjects: Animals; ATP-Binding Cassette, Sub-Family B, Member 1 - chemistry; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; ATP-Binding Cassette, Sub-Family B, Member 1 - physiology; Drug Resistance, Multiple; Humans; multidrug resistance / ABC superfamily / substrate binding / fluorescence quenching / resonance energy transfer; multidrug transporter; Protein Conformation; Spectrometry, Fluorescence; Structure-Activity Relationship
• ISSN: 1084-9521; 1096-3634
• DOI: 10.1006/scdb.2000.0251

P-glycoprotein is an ABC protein that functions as an efflux pump for multiple drugs, natural products and peptides. It is proposed to operate as a hydrophobic vacuum cleaner, expelling non-polar compounds from the membrane bilayer to the exterior, driven by the energy of ATP hydrolysis. The nucleotide-binding domains of P-glycoprotein appear to operate by an alternating sites mechanism to power drug transport. In recent years, purification and functional reconstitution of the protein has allowed the application of fluorescence spectroscopic techniques. This approach has led to insights into the structural architecture of the P-glycoprotein molecule, and a more detailed understanding of the way in which it interacts with nucleotides and drugs.