This Article Full Text Full Text (PDF) Supplement All Versions of this Article: biophysj.107.107482v1 93/4/1093    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Varma, S. Articles by Rempe, S. B. Search for Related Content PubMed PubMed Citation Articles by Varma, S. Articles by Rempe, S. B.

Tuning Ion Coordination Architectures to Enable Selective Partitioning

Computational Bioscience Department, Sandia National Laboratories, Albuquerque, New Mexico 87185

Correspondence: Address reprint requests to Susan B. Rempe, MS 0895, PO Box 5800, Albuquerque, NM 87185. Tel.: 505-845-0253; Fax: 505-284-3775; E-mail: slrempe{at}sandia.gov.

K⁺ ions seemingly permeate K-channels rapidly because channel binding sites mimic coordination of K⁺ ions in water. Highly selective ion discrimination should occur when binding sites form rigid cavities that match K⁺, but not the smaller Na⁺, ion size or when binding sites are composed of specific chemical groups. Although conceptually attractive, these views cannot account for critical observations: 1), K⁺ hydration structures differ markedly from channel binding sites; 2), channel thermal fluctuations can obscure sub-Ångström differences in ion sizes; and 3), chemically identical binding sites can exhibit diverse ion selectivities. Our quantum mechanical studies lead to a novel paradigm that reconciles these observations. We find that K-channels utilize a "phase-activated" mechanism where the local environment around the binding sites is tuned to sustain high coordination numbers (>6) around K⁺ ions, which otherwise are rarely observed in liquid water. When combined with the field strength of carbonyl ligands, such high coordinations create the electrical scenario necessary for rapid and selective K⁺ partitioning. Specific perturbations to the local binding site environment with respect to strongly selective K-channels result in altered K⁺/Na⁺ selectivities.

This article has been cited by other articles:

				R. Roth, D. Gillespie, W. Nonner, and R. E. Eisenberg Bubbles, Gating, and Anesthetics in Ion Channels Biophys. J., June 1, 2008; 94(11): 4282 - 4298. [Abstract] [Full Text] [PDF]

				G. M. Lipkind and H. A. Fozzard Voltage-gated Na Channel Selectivity: The Role of the Conserved Domain III Lysine Residue J. Gen. Physiol., May 26, 2008; 131(6): 523 - 529. [Full Text] [PDF]

				I. Schroeder and U.-P. Hansen Tl+-induced {micro}s Gating of Current Indicates Instability of the MaxiK Selectivity Filter as Caused by Ion/Pore Interaction J. Gen. Physiol., March 31, 2008; 131(4): 365 - 378. [Abstract] [Full Text] [PDF]

				D. Gillespie Energetics of Divalent Selectivity in a Calcium Channel: The Ryanodine Receptor Case Study Biophys. J., February 15, 2008; 94(4): 1169 - 1184. [Abstract] [Full Text] [PDF]

				M. Thomas, D. Jayatilaka, and B. Corry The Predominant Role of Coordination Number in Potassium Channel Selectivity Biophys. J., October 15, 2007; 93(8): 2635 - 2643. [Abstract] [Full Text] [PDF]

				P. C. Jordan Tuning a Potassium Channel The Caress of the Surroundings Biophys. J., August 15, 2007; 93(4): 1091 - 1092. [Full Text] [PDF]