Nature Structural & Molecular Biology 13, 311 - 318 (2006)
Published online: 12 March 2006; | doi:10.1038/nsmb1069
Molecular determinants of gating at the potassium-channel selectivity filterJulio F Cordero-Morales1, 3, Luis G Cuello1, 3, Yanxiang Zhao2, Vishwanath Jogini2, 3, D Marien Cortes1, 3, Benoît Roux2, 3
& Eduardo Perozo1, 31
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22906, USA. 2
Department of Physiology & Biophysics, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10021, USA. 3
Present address: Institute of Molecular Pediatrics Science and Department of Biochemistry and Molecular Biology, University of Chicago, Center for Integrative Science, 929 East 57th Street, Chicago, Illinois 60637, USA.
Correspondence should be addressed to Eduardo Perozo eperozo@virginia.edu We show that in the potassium channel KcsA, proton-dependent activation is followed by an inactivation process similar to C-type inactivation, and this process is suppressed by an E71A mutation in the pore helix. EPR spectroscopy demonstrates that the inner gate opens maximally at low pH regardless of the magnitude of the single-channel-open probability, implying that stationary gating originates mostly from rearrangements at the selectivity filter. Two E71A crystal structures obtained at 2.5 Å reveal large structural excursions of the selectivity filter during ion conduction and provide a glimpse of the range of conformations available to this region of the channel during gating. These data establish a mechanistic basis for the role of the selectivity filter during channel activation and inactivation.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
