期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 139, 期 26, 页码 8837-8845出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.7b01594
关键词
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资金
- U.S. National Institutes of Health [NIH DK079895, NIH R01-GM062342, NIH GM087546, NIH R01-GM057846]
- Membrane Protein Structural Dynamics Consortium [U54 GM087519]
The interplay between the intracellular gate and the selectivity filter underlies the structural basis for gating in potassium ion channels. Using a combination of protein semisynthesis, two-dimensional infrared (2D IR) spectroscopy, and molecular dynamics (MD) simulations, we probe the ion occupancy at the S1 binding site in the constricted state of the selectivity filter of the KcsA channel when the intracellular gate is open and closed. The 2D IR spectra resolve two features, whose relative intensities depend on the state of the intracellular gate. By matching the experiment to calculated 2D IR spectra of structures predicted by MD simulations, we identify the two features as corresponding to states with S1 occupied or unoccupied by K+. We learn that S1 is >70% occupied when the intracellular gate is closed and <15% occupied when the gate is open. Comparison of MD trajectories show that opening of the intracellular gate causes a structural change in the selectivity filter, which leads to a change in the ion occupancy. This work reveals the complexity of the conformational landscape of the K+ channel selectivity filter and its dependence on the state of the intracellular gate.
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