5UJA

Cryo-EM structure of bovine multidrug resistance protein 1 (MRP1) bound to leukotriene C4

Summary for 5UJA

• Entry DOI: 10.2210/pdb5uja/pdb
• Related: 5UJ9
• EMDB information: 8559 8560
• Descriptor: bovine multidrug resistance protein 1 (MRP1),Multidrug resistance-associated protein 1, (5~{S},6~{R},7~{E},9~{E},11~{Z},14~{Z})-6-[(2~{R})-2-[[(4~{S})-4-azanyl-5-oxidanyl-5-oxidanylidene-pentanoyl]amino]-3-( 2-hydroxy-2-oxoethylamino)-3-oxidanylidene-propyl]sulfanyl-5-oxidanyl-icosa-7,9,11,14-tetraenoic acid (2 entities in total)
• Functional Keywords: abc transporter, multidrug resistance, leukotriene c4, ltc4, protein transport
• Biological source: Bos taurus; More
• Total number of polymer chains: 1
• Total formula weight: 160327.70

Authors

Johnson, Z.L.,Chen, J. (deposition date: 2017-01-17, release date: 2017-02-22, Last modification date: 2024-03-13)

Primary citation

Johnson, Z.L.,Chen, J.
Structural Basis of Substrate Recognition by the Multidrug Resistance Protein MRP1.
Cell, 168:1075-1085.e9, 2017

PubMed 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 C. 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 C, 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.

PubMed: 28238471
DOI: 10.1016/j.cell.2017.01.041

Experimental method

ELECTRON MICROSCOPY (3.34 Å)