This Article Full Text Full Text (PDF) 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 Miloshevsky, G. V. Articles by Jordan, P. C. Search for Related Content PubMed PubMed Citation Articles by Miloshevsky, G. V. Articles by Jordan, P. C.

Gating Gramicidin Channels in Lipid Bilayers: Reaction Coordinates and the Mechanism of Dissociation

Department of Chemistry, Brandeis University, Waltham, Massachusetts

Correspondence: Address reprint requests to Peter C. Jordan, Dept. of Chemistry, MS-015, Brandeis University, P.O. Box 549110, Waltham, MA 02454-9110. Tel.: 781-736-2540; E-mail: jordan{at}brandeis.edu.

The dissociation of gramicidin A (gA) channels into monomers is the simplest example of a channel gating process. The initial steps in this process are studied via a computational model that simulates the reaction coordinate for dimer-monomer dissociation. The nonbonded interaction energy between the monomers is determined, allowing for their free relative translational and rotational motion. Lowest energy pathways and reaction coordinates of the gating process are determined. Partial rupture of the six hydrogen bonds (6HB) at the dimer junction takes place by coupling monomer rotation and lateral displacement. Coupling rotation with axial separation is far more expensive energetically. The transition state for channel dissociation occurs when monomers are displaced laterally by 4–6 Å, separated by 1.6–2 Å, and rotated by 120°, breaking two hydrogen bonds. In membranes with significant hydrophobic mismatch there is a much greater likelihood of forming 4HB and possibly even 2HB states. In the 4HB state the pore remains fully open and conductive. However, transitions from the 6HB to 4HB and 4HB to 2HB states take place via intermediates in which the gA pore is closed and nonconductive. These lateral monomer displacements give rise to transitory pore occlusion at the dimer junction, which provides a rationale for fast closure events (flickers). Local dynamics of gA monomers also leads to lateral and rotational diffusion of the whole gA dimer, giving rise to diffusional rotation of the dimer about the channel axis.

This article has been cited by other articles:

				J. A. Lundbaek Lipid Bilayer-mediated Regulation of Ion Channel Function by Amphiphilic Drugs J. Gen. Physiol., April 28, 2008; 131(5): 421 - 429. [Full Text] [PDF]

				G. V. Miloshevsky and P. C. Jordan Water and Ion Permeation in bAQP1 and GlpF Channels: A Kinetic Monte Carlo Study Biophys. J., December 1, 2004; 87(6): 3690 - 3702. [Abstract] [Full Text] [PDF]

				G. V. Miloshevsky and P. C. Jordan Anion Pathway and Potential Energy Profiles along Curvilinear Bacterial ClC Cl- Pores: Electrostatic Effects of Charged Residues Biophys. J., February 1, 2004; 86(2): 825 - 835. [Abstract] [Full Text] [PDF]