Error message

No crossref credentials set for sci

Ion Selectivity in a Semisynthetic K+ Channel Locked in the Conductive Conformation

Science, 10 November 2006
Vol. 314, Issue 5801, p. 1004-1007
DOI: 10.1126/science.1133415

Ion Selectivity in a Semisynthetic K+ Channel Locked in the Conductive Conformation

  1. Francis I. Valiyaveetil*,
  2. Manuel Leonetti,
  3. Tom W. Muir,
  4. Roderick MacKinnon
  1. Laboratories of Molecular Neurobiology and Biophysics and Synthetic Protein Chemistry, Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10021, USA, and Department of Biology, Ecole Normale Superieure, 46 rue d'Ulm, 75005 Paris, France.
  1. To whom correspondence should be addressed. E-mail: mackinn{at} (R.M.), muirt{at} (T.W.M.)
  • * Present address: Department of Physiology and Pharmacology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Mail Code L334, Portland, OR 97239, USA.


Potassium channels are K+-selective protein pores in cell membrane. The selectivity filter is the functional unit that allows K+ channels to distinguish potassium (K+) and sodium (Na+) ions. The filter's structure depends on whether K+ or Na+ ions are bound inside it. We synthesized a K+ channel containing the d-enantiomer of alanine in place of a conserved glycine and found by x-ray crystallography that its filter maintains the K+ (conductive) structure in the presence of Na+ and very low concentrations of K+. This channel conducts Na+ in the absence of K+ but not in the presence of K+. These findings demonstrate that the ability of the channel to adapt its structure differently to K+ and Na+ is a fundamental aspect of ion selectivity, as is the ability of multiple K+ ions to compete effectively with Na+ for the conductive filter.

    • Received for publication 3 August 2006.
    • Accepted for publication 10 October 2006.


    F. I. Valiyaveetil, M. Leonetti, T. W. Muir, and R. MacKinnon, Ion Selectivity in a Semisynthetic K+ Channel Locked in the Conductive Conformation. Science 314, 1004-1007 (2006).

    Mitochondrial Channels: Ion Fluxes and More
    I. Szabo, and M. Zoratti
    Physiol. Rev. 94, 519-608 (1 April 2014)

    Semisynthetic K+ channels show that the constricted conformation of the selectivity filter is not the C-type inactivated state
    P. K. Devaraneni, A. G. Komarov, C. A. Costantino, J. J. Devereaux, K. Matulef, and F. I. Valiyaveetil
    Proc. Natl. Acad. Sci. USA 110, 15698-15703 (24 September 2013)

    Preferential binding of K+ ions in the selectivity filter at equilibrium explains high selectivity of K+ channels
    S. Liu, X. Bian, and S. W. Lockless
    JGP 140, 671-679 (26 November 2012)

    Ferritin Protein Nanocage Ion Channels: GATING BY N-TERMINAL EXTENSIONS
    T. Tosha, R. K. Behera, H.-L. Ng, O. Bhattasali, T. Alber, and E. C. Theil
    J Biol Chem 287, 13016-13025 (13 April 2012)

    Thermodynamic coupling between activation and inactivation gating in potassium channels revealed by free energy molecular dynamics simulations
    A. C. Pan, L. G. Cuello, E. Perozo, and B. Roux
    JGP 138, 571-580 (1 December 2011)

    Protein interactions central to stabilizing the K+ channel selectivity filter in a four-sited configuration for selective K+ permeation
    D. B. Sauer, W. Zeng, S. Raghunathan, and Y. Jiang
    Proc. Natl. Acad. Sci. USA 108, 16634-16639 (4 October 2011)

    Perspectives on: Ion selectivity: Design principles for K+ selectivity in membrane transport
    S. Varma, D. M. Rogers, L. R. Pratt, and S. B. Rempe
    JGP 137, 479-488 (30 May 2011)

    Activity-dependent targeting of TRPV1 with a pore-permeating capsaicin analog
    H. Li, S. Wang, A. Y. Chuang, B. E. Cohen, and H.-h. Chuang
    Proc. Natl. Acad. Sci. USA 108, 8497-8502 (17 May 2011)

    Perspectives on: Ion selectivity: Ion selectivity in channels and transporters
    B. Roux, S. Berneche, B. Egwolf, B. Lev, S. Y. Noskov, C. N. Rowley, and H. Yu
    JGP 137, 415-426 (1 May 2011)

    Perspectives on: Ion selectivity: Origins of ion selectivity in potassium channels from the perspective of channel block
    C. M. Nimigean, and T. W. Allen
    JGP 137, 405-413 (25 April 2011)

    Perspectives on: Ion selectivity: Thermodynamics of ion selectivity in the KcsA K+ channel
    P. D. Dixit, and D. Asthagiri
    JGP 137, 427-433 (25 April 2011)

    Perspectives on: Ion selectivity: Structural studies of ion selectivity in tetrameric cation channels
    A. Alam, and Y. Jiang
    JGP 137, 397-403 (25 April 2011)

    Mechanism for selectivity-inactivation coupling in KcsA potassium channels
    W. W. L. Cheng, J. G. McCoy, A. N. Thompson, C. G. Nichols, and C. M. Nimigean
    Proc. Natl. Acad. Sci. USA 108, 5272-5277 (29 March 2011)

    Tuning the ion selectivity of tetrameric cation channels by changing the number of ion binding sites
    M. G. Derebe, D. B. Sauer, W. Zeng, A. Alam, N. Shi, and Y. Jiang
    Proc. Natl. Acad. Sci. USA 108, 598-602 (11 January 2011)

    Two mechanisms of ion selectivity in protein binding sites
    H. Yu, S. Y. Noskov, and B. Roux
    Proc. Natl. Acad. Sci. USA 107, 20329-20334 (23 November 2010)

    Principles of conduction and hydrophobic gating in K+ channels
    M. O. Jensen, D. W. Borhani, K. Lindorff-Larsen, P. Maragakis, V. Jogini, M. P. Eastwood, R. O. Dror, and D. E. Shaw
    Proc. Natl. Acad. Sci. USA 107, 5833-5838 (30 March 2010)

    Tetramerization domain mutations in KCNA5 affect channel kinetics and cause abnormal trafficking patterns
    E. D. Burg, O. Platoshyn, I. F. Tsigelny, B. Lozano-Ruiz, B. K. Rana, and J. X.-J. Yuan
    Am. J. Physiol. Cell Physiol. 298, C496-C509 (1 March 2010)

    Lotus japonicus CASTOR and POLLUX Are Ion Channels Essential for Perinuclear Calcium Spiking in Legume Root Endosymbiosis
    M. Charpentier, R. Bredemeier, G. Wanner, N. Takeda, E. Schleiff, and M. Parniske
    Plant Cell 20, 3467-3479 (1 December 2008)

    Gating at the selectivity filter in cyclic nucleotide-gated channels
    J. E. Contreras, D. Srikumar, and M. Holmgren
    Proc. Natl. Acad. Sci. USA 105, 3310-3314 (4 March 2008)

    Ion binding in the Open HCN Pacemaker Channel Pore: Fast Mechanisms to Shape "Slow" Channels
    A. K. Lyashchenko, and G. R. Tibbs
    JGP 131, 227-243 (25 February 2008)

    Selectivity in K+ channels is due to topological control of the permeant ion's coordinated state
    D. L. Bostick, and C. L. Brooks
    Proc. Natl. Acad. Sci. USA 104, 9260-9265 (29 May 2007)

    Highlights From The Literature
    C. L. Brooks
    Physiology 22, 70-72 (1 April 2007)

    Importance of Hydration and Dynamics on the Selectivity of the KcsA and NaK Channels
    S. Yu. Noskov, and B. Roux
    JGP 129, 135-143 (29 January 2007)

    Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882