This Article Full Text Full Text (PDF) Supplemental All Versions of this Article: biophysj.105.080093v1 90/11/3929    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 Shrivastava, I. H. Articles by Bahar, I. Search for Related Content PubMed PubMed Citation Articles by Shrivastava, I. H. Articles by Bahar, I.

Common Mechanism of Pore Opening Shared by Five Different Potassium Channels

Department of Computational Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

Correspondence: Address reprint requests to Ivet Bahar, Dept. of Computational Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213. E-mail: bahar{at}ccbb.pitt.edu.

A fundamental question associated with the function of ion channels is the conformational changes that allow for reversibly opening/occluding the pore through which the cations permeate. The recently elucidated crystal structures of potassium channels reveal similar structural motifs at their pore-forming regions, suggesting that they share a common gating mechanism. The validity of this hypothesis is explored by analyzing the collective dynamics of five known K⁺ channel structures. Normal-mode analysis using the Gaussian network model strikingly reveals that all five structures display the same intrinsic motions at their pore-forming region despite the differences in their sequences, structures, and activation mechanisms. Superposition of the most cooperative mode profiles shows that the identified common mechanism is a global corkscrew-like counterrotation of the extracellular and cytoplasmic (CP) regions, leading to the opening of the CP end of the pore. A second cooperative mode shared by all five K⁺ channels is the extension of the extracellular and/or CP ends via alternating anticorrelated fluctuations of pairs of diagonally opposite monomers. Residues acting as hinges/anchors in both modes are highly conserved across the members of the family of K⁺ channel proteins, consistent with their presently disclosed critical mechanical role in pore gating.

This article has been cited by other articles:

				R. J. Mashl and E. Jakobsson End-Point Targeted Molecular Dynamics: Large-Scale Conformational Changes in Potassium Channels Biophys. J., June 1, 2008; 94(11): 4307 - 4319. [Abstract] [Full Text] [PDF]

				S. Vemparala, C. Domene, and M. L. Klein Interaction of Anesthetics with Open and Closed Conformations of a Potassium Channel Studied via Molecular Dynamics and Normal Mode Analysis Biophys. J., June 1, 2008; 94(11): 4260 - 4269. [Abstract] [Full Text] [PDF]

				T. Z. Sen, M. Kloster, R. L. Jernigan, A. Kolinski, J. M. Bujnicki, and A. Kloczkowski Predicting the Complex Structure and Functional Motions of the Outer Membrane Transporter and Signal Transducer FecA Biophys. J., April 1, 2008; 94(7): 2482 - 2491. [Abstract] [Full Text] [PDF]

				W. Zheng, B. R. Brooks, and D. Thirumalai Allosteric Transitions in the Chaperonin GroEL are Captured by a Dominant Normal Mode that is Most Robust to Sequence Variations Biophys. J., October 1, 2007; 93(7): 2289 - 2299. [Abstract] [Full Text] [PDF]

				A. Szarecka, Y. Xu, and P. Tang Dynamics of Firefly Luciferase Inhibition by General Anesthetics: Gaussian and Anisotropic Network Analyses Biophys. J., September 15, 2007; 93(6): 1895 - 1905. [Abstract] [Full Text] [PDF]