6UY0

Cryo-EM structure of wild-type bovine multidrug resistance protein 1 (MRP1) under active turnover conditions

Summary for 6UY0

• Entry DOI: 10.2210/pdb6uy0/pdb
• Related: 5UJ9 5UJA 6BHU
• EMDB information: 20945 7099 8559 8560
• Descriptor: Multidrug resistance-associated protein 1, ADENOSINE-5'-TRIPHOSPHATE, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: abc transporter, multidrug resistance, outward facing, transport protein, mrp1
• Biological source: Bos taurus (Bovine)
• Total number of polymer chains: 1
• Total formula weight: 175005.52

Authors

Johnson, Z.L.,Chen, J. (deposition date: 2019-11-09, release date: 2020-06-10, Last modification date: 2024-03-06)

Primary citation

Wang, L.,Johnson, Z.L.,Wasserman, M.R.,Levring, J.,Chen, J.,Liu, S.
Characterization of the kinetic cycle of an ABC transporter by single-molecule and cryo-EM analyses.
Elife, 9:-, 2020

PubMed Abstract: ATP-binding cassette (ABC) transporters are molecular pumps ubiquitous across all kingdoms of life. While their structures have been widely reported, the kinetics governing their transport cycles remain largely unexplored. Multidrug resistance protein 1 (MRP1) is an ABC exporter that extrudes a variety of chemotherapeutic agents and native substrates. Previously, the structures of MRP1 were determined in an inward-facing (IF) or outward-facing (OF) conformation. Here, we used single-molecule fluorescence spectroscopy to track the conformational changes of bovine MRP1 (bMRP1) in real time. We also determined the structure of bMRP1 under active turnover conditions. Our results show that substrate stimulates ATP hydrolysis by accelerating the IF-to-OF transition. The rate-limiting step of the transport cycle is the dissociation of the nucleotide-binding-domain dimer, while ATP hydrolysis per se does not reset MRP1 to the resting state. The combination of structural and kinetic data illustrates how different conformations of MRP1 are temporally linked and how substrate and ATP alter protein dynamics to achieve active transport.

PubMed: 32458799
DOI: 10.7554/eLife.56451

Experimental method

ELECTRON MICROSCOPY (3.23 Å)