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Recovery from slow inactivation in K+ channels is controlled by water molecules

Author

Listed:
  • Jared Ostmeyer

    (The University of Chicago, 929 E57th Street, Chicago, Illinois 60637, USA)

  • Sudha Chakrapani

    (School of Medicine, Case Western Reserve University)

  • Albert C. Pan

    (The University of Chicago, 929 E57th Street, Chicago, Illinois 60637, USA
    Present address: D. E. Shaw Research, New York, New York 10036, USA.)

  • Eduardo Perozo

    (The University of Chicago, 929 E57th Street, Chicago, Illinois 60637, USA)

  • Benoît Roux

    (The University of Chicago, 929 E57th Street, Chicago, Illinois 60637, USA)

Abstract

A series of long molecular dynamics simulations shows that the K+ channel is sterically locked in the inactive conformation by buried water molecules bound behind the selectivity filter; a kinetic model deduced from the simulations shows how releasing the buried waters can elongate the timescale of the recovery period, and this hypothesis is confirmed using ‘wet’ biophysical experiments.

Suggested Citation

  • Jared Ostmeyer & Sudha Chakrapani & Albert C. Pan & Eduardo Perozo & Benoît Roux, 2013. "Recovery from slow inactivation in K+ channels is controlled by water molecules," Nature, Nature, vol. 501(7465), pages 121-124, September.
    • Handle: RePEc:nat:nature:v:501:y:2013:i:7465:d:10.1038_nature12395
    DOI: 10.1038/nature12395
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    Cited by:

    1. Carus H. Y. Lau & Emelie Flood & Mark J. Hunter & Billy J. Williams-Noonan & Karen M. Corbett & Chai-Ann Ng & James C. Bouwer & Alastair G. Stewart & Eduardo Perozo & Toby W. Allen & Jamie I. Vandenbe, 2024. "Potassium dependent structural changes in the selectivity filter of HERG potassium channels," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Ahmed Rohaim & Bram J. A. Vermeulen & Jing Li & Felix Kümmerer & Federico Napoli & Lydia Blachowicz & João Medeiros-Silva & Benoît Roux & Markus Weingarth, 2022. "A distinct mechanism of C-type inactivation in the Kv-like KcsA mutant E71V," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Anh T. P. Nguyen & Austin T. Weigle & Diwakar Shukla, 2024. "Functional regulation of aquaporin dynamics by lipid bilayer composition," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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