Mudança paradigmática no entendimento dos canais de potássio: mais design inteligente!

sexta-feira, outubro 17, 2014

Science 17 October 2014: 
Vol. 346 no. 6207 pp. 352-355 
DOI: 10.1126/science.1254840
Ion permeation in K+ channels occurs by direct Coulomb knock-on

David A. Köpfer1,†, Chen Song2,*,†, Tim Gruene3, George M. Sheldrick3, Ulrich Zachariae4,5,*,‡, Bert L. de Groot1,*,‡

- Author Affiliations

1Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
2Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
3Department of Structural Chemistry, University of Göttingen, 37077 Göttingen, Germany.
4School of Engineering, Physics and Mathematics, University of Dundee, Dundee DD1 4HN, UK.
5College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.

↵*Corresponding author. E-mail: (C.S.); (U.Z.); (B.L.d.G.)

↵† These authors contributed equally to this work.

↵‡ These authors contributed equally to this work.


Potassium channels selectively conduct K+ ions across cellular membranes with extraordinary efficiency. Their selectivity filter exhibits four binding sites with approximately equal electron density in crystal structures with high K+ concentrations, previously thought to reflect a superposition of alternating ion- and water-occupied states. Consequently, cotranslocation of ions with water has become a widely accepted ion conduction mechanism for potassium channels. By analyzing more than 1300 permeation events from molecular dynamics simulations at physiological voltages, we observed instead that permeation occurs via ion-ion contacts between neighboring K+ ions. Coulomb repulsion between adjacent ions is found to be the key to high-efficiency K+ conduction. Crystallographic data are consistent with directly neighboring K+ ions in the selectivity filter, and our model offers an intuitive explanation for the high throughput rates of K+ channels.

Received for publication 15 April 2014.

Accepted for publication 27 August 2014.



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