Related Experiment Video
Updated: Mar 7, 2026

Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein
Published on: December 3, 2010
Structural Basis of Substrate Recognition by the Multidrug Resistance Protein MRP1
Zachary Lee Johnson1, Jue Chen1
1Laboratory of Membrane Biology and Biophysics, The Rockefeller University and the Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.
Abstract:
The multidrug resistance protein MRP1 is an ATP-binding cassette (ABC) transporter that confers resistance to many anticancer drugs and plays a role in the disposition and efficacy of several opiates, antidepressants, statins, and antibiotics. In addition, MRP1 regulates redox homeostasis, inflammation, and hormone secretion. Using electron cryomicroscopy, we determined the molecular structures of bovine MRP1 in two conformations: an apo form at 3.5 Å without any added substrate and a complex form at 3.3 Å with one of its physiological substrates, leukotriene C4. These structures show that by forming a single bipartite binding site, MRP1 can recognize a spectrum of substrates with different chemical structures. We also observed large conformational changes induced by leukotriene C4, explaining how substrate binding primes the transporter for ATP hydrolysis. Structural comparison of MRP1 and P-glycoprotein advances our understanding of the common and unique properties of these two important molecules in multidrug resistance to chemotherapy.
Related Concept Videos
Directing Proteins to the Rough Endoplasmic Reticulum
Insertion of Multi-pass Transmembrane Proteins in the RER
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
Carrier-Mediated Transport
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
The Significance of Membrane Transport
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Export of Misfolded Proteins out of the ER

