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Biophys. J. BioFAST: First Published August 17, 2007. doi:10.1529/biophysj.107.112540
© 2007 by the Biophysical Society.

A more recent version of this article appeared on November 1, 2007.
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CHANNELS, RECEPTORS, AND ELECTRICAL SIGNALING

Dynamics of the Kv1.2 voltage-gated K+ channel in a Membrane Environment

Vishwanath Jogini 1 and Benoit Roux 1*

1 The University of Chicago

* To whom correspondence should be addressed. E-mail: roux{at}uchicago.edu.

Submitted on May 11, 2007
Revised on June 13, 2007
Accepted on 20 June 2007


  Abstract
All-atom MD simulations are used to better understand the dynamic environment experienced by the Kv1.2 channel in a lipid membrane. The structure of the channel is stable during the trajectories. The pore domain keeps a well-defined conformation while the voltage-sensing domains undergo important lateral fluctuations, consistent with their modular nature. A channel-like region at the center of the S1-S4 helical bundle fills rapidly by water, reminiscent of the concept of high dielectric aqueous crevices. The first two arginines along S4 (R294 and R297) adopt an interfacial position where they interact favorably with water and the lipid headgroups. The following two arginines (R300 and R303) interact predominantly with water and E226 in S2. Despite the absence of a structurally permanent gating pore formed by protein residues and surrounding the S4 helix as traditionally pictured, the charged residues are located in a favorable environment and are not extensively exposed to the membrane nonpolar region. Continuum electrostatic computations indicate that the transmembrane potential sensed by the charged residues in the voltage sensor varies abruptly over the outer half of the membrane in the arginine-rich region of S4, thus, the voltage gradient or membrane electric field is "focused". Interactions of basic residues with the lipid headgroups at the intracellular membrane-solution interface reduce the membrane thickness near the channel, resulting in an increased transmembrane field.

Key Words: arginine, electrostatics, free energy, membrane voltage, phospholipid, solvation




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Copyright © 2007 by the Biophysical Society.