Format

Send to

Choose Destination
Nat Chem. 2018 Aug;10(8):813-820. doi: 10.1038/s41557-018-0105-9. Epub 2018 Jul 20.

Direct knock-on of desolvated ions governs strict ion selectivity in K+ channels.

Author information

1
Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
2
Computational Biology, School of Life Sciences, University of Dundee, Dundee, UK.
3
Physics, School of Science and Engineering, University of Dundee, Dundee, UK.
4
University of Groningen, Zernike Institute for Advanced Materials, Groningen, The Netherlands.
5
Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany. bgroot@gwdg.de.
6
Computational Biology, School of Life Sciences, University of Dundee, Dundee, UK. u.zachariae@dundee.ac.uk.
7
Physics, School of Science and Engineering, University of Dundee, Dundee, UK. u.zachariae@dundee.ac.uk.

Abstract

The seeming contradiction that K+ channels conduct K+ ions at maximal throughput rates while not permeating slightly smaller Na+ ions has perplexed scientists for decades. Although numerous models have addressed selective permeation in K+ channels, the combination of conduction efficiency and ion selectivity has not yet been linked through a unified functional model. Here, we investigate the mechanism of ion selectivity through atomistic simulations totalling more than 400 μs in length, which include over 7,000 permeation events. Together with free-energy calculations, our simulations show that both rapid permeation of K+ and ion selectivity are ultimately based on a single principle: the direct knock-on of completely desolvated ions in the channels' selectivity filter. Herein, the strong interactions between multiple 'naked' ions in the four filter binding sites give rise to a natural exclusion of any competing ions. Our results are in excellent agreement with experimental selectivity data, measured ion interaction energies and recent two-dimensional infrared spectra of filter ion configurations.

Comment in

PMID:
30030538
DOI:
10.1038/s41557-018-0105-9
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center