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

TY - JOUR

T1 - Direct knock-on of desolvated ions governs strict ion selectivity in K+ channels

AU - Kopec, Wojciech

AU - Köpfer, David A.

AU - Vickery, Owen N.

AU - Bondarenko, Anna S.

AU - Jansen, Thomas L.C.

AU - De Groot, Bert L.

AU - Zachariae, Ulrich

N1 - We thank Helmut Grubmüller, Simon Bernèche, Florian Heer and Salomé Llabrés for helpful discussions. Supported by the German Research Foundation DFG through FOR 2518 ‘DynIon’, Project P5 (W.K. and B.L.d.G), the Scottish Universities’ Physics Alliance (U.Z.) and the BBSRC (training grant BB/J013072/1, O.N.V. and U.Z.). All data and analysis scripts are archived at the Max Planck Institute for Biophysical Chemistry archives and available upon request.

PY - 2018/7/20

Y1 - 2018/7/20

N2 - The seeming contradiction that K+ channels conduct K+ ions at maximal throughput rates while not permeating the slightly smaller Na+ ion 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 microseconds in length, which include over 7000 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 twodimensional infrared spectra of filter ion configurations.

AB - The seeming contradiction that K+ channels conduct K+ ions at maximal throughput rates while not permeating the slightly smaller Na+ ion 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 microseconds in length, which include over 7000 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 twodimensional infrared spectra of filter ion configurations.

U2 - 10.1038/s41557-018-0105-9

DO - 10.1038/s41557-018-0105-9

M3 - Article

C2 - 30030538

SN - 1755-4330

VL - 10

SP - 813

EP - 820

JO - Nature Chemistry

JF - Nature Chemistry

IS - 8

ER -