Arne Moeller / Sung Chang Lee / Houchao Tao / Jeffrey A Speir / Geoffrey Chang / Ina L Urbatsch / Clinton S Potter / Bridget Carragher / Qinghai Zhang /
PubMed Abstract
ATP-binding cassette (ABC) exporters are ubiquitously found in all kingdoms of life and their members play significant roles in mediating drug pharmacokinetics and multidrug resistance in the clinic. ...ATP-binding cassette (ABC) exporters are ubiquitously found in all kingdoms of life and their members play significant roles in mediating drug pharmacokinetics and multidrug resistance in the clinic. Significant questions and controversies remain regarding the relevance of their conformations observed in X-ray structures, their structural dynamics, and mechanism of transport. Here, we used single particle electron microscopy (EM) to delineate the entire conformational spectrum of two homologous ABC exporters (bacterial MsbA and mammalian P-glycoprotein) and the influence of nucleotide and substrate binding. Newly developed amphiphiles in complex with lipids that support high protein stability and activity enabled EM visualization of individual complexes in a membrane-mimicking environment. The data provide a comprehensive view of the conformational flexibility of these ABC exporters under various states and demonstrate not only similarities but striking differences between their mechanistic and energetic regulation of conformational changes.
EMDB-6007: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 40.0 Å
EMDB-6018: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 30.0 Å
EMDB-6019: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 40.0 Å
EMDB-6020: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 30.0 Å
EMDB-6021: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 30.0 Å
EMDB-6022: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 30.0 Å
EMDB-6023: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 30.0 Å
EMDB-6024: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 30.0 Å
EMDB-6025: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 30.0 Å
EMDB-6026: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 30.0 Å
EMDB-6027: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 30.0 Å
EMDB-6028: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 30.0 Å
EMDB-6029: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 30.0 Å
EMDB-6030: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 30.0 Å
EMDB-6031: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 30.0 Å
EMDB-6032: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 30.0 Å
EMDB-6033: Conformational Spectrum of Multidrug ABC Transporters Revealed by Single Particle Electron Microscopy Method: EM (single particle) / Resolution: 30.0 Å
Source
Mus musculus (house mouse)
Escherichia coli (E. coli)
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