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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Moeller, Arne Lee, Sung Chang Tao, Houchao Speir, Jeffrey A. Chang, Geoffrey Urbatsch, Ina L. Potter, Clinton S. Carragher, Bridget Zhang, Qinghai |
| Description | Country affiliation: United States Author Affiliation: Moeller A ( Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA); Lee SC ( Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.); Tao H ( Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.); Speir JA ( Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA); Chang G ( Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.); Urbatsch IL ( Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA.); Potter CS ( Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA); Carragher B ( Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA); Zhang Q ( Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: qinghai@scripps.edu.) |
| 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. 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. |
| File Format | HTM / HTML |
| ISSN | 09692126 |
| e-ISSN | 18784186 |
| DOI | 10.1016/j.str.2014.12.013 |
| Journal | Structure |
| Issue Number | 3 |
| Volume Number | 23 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2015-03-03 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Molecular Biology Discipline Biochemistry Discipline Biotechnology Atp-binding Cassette Transporters Ultrastructure Bacterial Proteins P-glycoprotein Chemistry Animals Membrane Lipids Mice Microscopy, Electron Models, Molecular Nucleotides Protein Binding Protein Conformation Protein Stability Structural Homology, Protein Research Support, N.i.h., Extramural |
| Content Type | Text |
| Resource Type | Article |
| Subject | Structural Biology Molecular Biology |
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