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Structural Basis of Energy Transduction in the Transport Cycle of MsbA
Jinhui Dong,Guangyong Yang,Hassane S. Mchaourab*
We used site-directed spin-labeling and electron paramagneticresonance spectroscopy to characterize the conformational motionthat couples energy expenditure to substrate translocation inthe multidrug transporter MsbA. In liposomes, ligand-free MsbAsamples conformations that depart from the crystal structures,including looser packing and water penetration along the periplasmicside. Adenosine triphosphate (ATP) binding closes the substratechamber to the cytoplasm while increasing hydration at the periplasmicside, consistent with an alternating access model. Accentuatedby ATP hydrolysis, the changes in the chamber dielectric environmentand its geometry provide the likely driving force for flippingamphipathic substrates and a potential exit pathway. These resultsestablish the structural dynamic basis of the power stroke inmultidrug-resistant ATP-binding cassette (MDR ABC) transporters.
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA.
* To whom correspondence should be addressed. E-mail: hassane.mchaourab{at}vanderbilt.edu
Amy L. Davidson and Jue Chen (13 May 2005) Science308 (5724), 963.
[DOI: 10.1126/science.1113414] |Summary »|Full Text »|PDF »
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