Molecular Determinants of Gating at the Potassium-Channel Selectivity Filter

Cordero-Morales, J; Cuello, L; Zhao, Y; Jogini, V; Cortes, D; Roux, B; Perozo, E

doi:10.1038/nsmb1069

Title: Molecular Determinants of Gating at the Potassium-Channel Selectivity Filter

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Abstract

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 Angstroms 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.

Authors:: Cordero-Morales, J; Cuello, L; Zhao, Y; Jogini, V; Cortes, D; Roux, B; Perozo, E

Publication Date:: Sun Jan 01 00:00:00 EST 2006

Research Org.:: Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source

Sponsoring Org.:: Doe - Office Of Science

OSTI Identifier:: 914011

Report Number(s):: BNL-78579-2007-JA
TRN: US0801472

DOE Contract Number:: DE-AC02-98CH10886

Resource Type:: Journal Article

Journal Name:: Nat. Struct. Mol. Biol.

Additional Journal Information:: Journal Volume: 13; Journal Issue: 4

Country of Publication:: United States

Language:: English

Subject:: 36 MATERIALS SCIENCE; 43 PARTICLE ACCELERATORS; CRYSTAL STRUCTURE; INACTIVATION; MUTATIONS; POTASSIUM; PROBABILITY; SPECTROSCOPY; NSLS; national synchrotron light source

Citation Formats


                    Cordero-Morales, J, Cuello, L, Zhao, Y, Jogini, V, Cortes, D, Roux, B, and Perozo, E. Molecular Determinants of Gating at the Potassium-Channel Selectivity Filter.  United States: N. p., 2006. 
        Web.  doi:10.1038/nsmb1069.

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                    Cordero-Morales, J, Cuello, L, Zhao, Y, Jogini, V, Cortes, D, Roux, B, & Perozo, E. Molecular Determinants of Gating at the Potassium-Channel Selectivity Filter.  United States.  https://doi.org/10.1038/nsmb1069

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                    Cordero-Morales, J, Cuello, L, Zhao, Y, Jogini, V, Cortes, D, Roux, B, and Perozo, E. 2006.  
        "Molecular Determinants of Gating at the Potassium-Channel Selectivity Filter".  United States.  https://doi.org/10.1038/nsmb1069.

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@article{osti_914011,

  title        = {Molecular Determinants of Gating at the Potassium-Channel Selectivity Filter},

  author       = {Cordero-Morales, J and Cuello, L and Zhao, Y and Jogini, V and Cortes, D and Roux, B and Perozo, E},

  abstractNote = {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 Angstroms 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.},

  doi          = {10.1038/nsmb1069},

  url          = {https://www.osti.gov/biblio/914011},
  journal      = {Nat. Struct. Mol. Biol.},
number       = 4,

  volume       = 13,

  place        = {United States},

  year         = {Sun Jan 01 00:00:00 EST 2006},

  month        = {Sun Jan 01 00:00:00 EST 2006}

}

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