Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The structure of the bacterial potassium channel, KcsA, corresponds to the channel in a closed state. Two lines of evidence suggest that the channel must widen its intracellular mouth when in an open state: 1) internal block by a series of tetraalkylammonium ions and 2) spin labeling experiments. Thus it is known that the protein moves in this region, but it is unclear by how much and the mechanisms that are involved. To address this issue we have applied a novel approach to generate plausible open-state models of KcsA. The approach can be thought of as placing a balloon inside the channel and gradually inflating it. Only the protein sees the balloon, and so water is free to move in and out of the channel. The balloon is a van der Waals sphere whose parameters change by a small amount at each time step, an approach similar to methods used in free energy perturbation calculations. We show that positioning of this balloon at various positions along the pore axis generates similar open-state models, thus indicating that there may be a preferred pathway to an open state. We also show that the resulting structures from this process are conformationally unstable and need to undergo a relaxation process for up to 4 ns. We show that the channel can relax into a new state that has a larger pore radius at the region of the intracellular mouth. The resulting models may be useful in exploring models of the channel in the context of ion permeation and blocking agents.

Original publication

DOI

10.1016/S0006-3495(02)73951-9

Type

Journal article

Journal

Biophys J

Publication Date

10/2002

Volume

83

Pages

1867 - 1876

Keywords

Bacterial Proteins, Biophysical Phenomena, Biophysics, Computer Simulation, Crystallography, X-Ray, Models, Molecular, Potassium Channels, Protein Conformation, Protein Structure, Secondary, Spin Labels, Time Factors