Dataset Information

Regulation of Ion Permeation of the KcsA Channel by Applied Midinfrared Field.

ABSTRACT: Ion transport molecules are involved in many physiological and pathological processes and are considered potential targets for cancer treatment. In the large family of ion transport molecules, potassium (K) ion channels, as surface-expressed proteins, show the highest variability and most frequent expression changes in many tumor types. The key to exploring the permeation of K⁺ through potassium channels lies in the conserved sequence TVGYG, which is common in the selectivity filter (SF) region of all potassium channels. We found that the K⁺ flux significantly increased with the help of a specific frequency terahertz electromagnetic wave (51.87 THz) in the KcsA channel using a molecular dynamics combined model through the combined simulation of the constant electric field method and ion imbalance method. This frequency has the strongest absorption peak in the infrared spectrum of -C=O groups in the SF region. With the applied electric field of 51.87 THz, the Y78 residue at the S₁ site of the SF has a smaller vibration amplitude and a more stable structure, which enables the K⁺ to bind closely with the carbonyl oxygen atoms in the SF and realize ion conduction in a more efficient direct Coulomb knock-on.

SUBMITTER: Wang Y

PROVIDER: S-EPMC9820211 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Regulation of Ion Permeation of the KcsA Channel by Applied Midinfrared Field.

Wang Yize Y Wang Hongguang H Ding Wen W Zhao Xiaofei X Li Yongdong Y Liu Chunliang C

International journal of molecular sciences 20221229 1

Ion transport molecules are involved in many physiological and pathological processes and are considered potential targets for cancer treatment. In the large family of ion transport molecules, potassium (K) ion channels, as surface-expressed proteins, show the highest variability and most frequent expression changes in many tumor types. The key to exploring the permeation of K<sup>+</sup> through potassium channels lies in the conserved sequence TVGYG, which is common in the selectivity filter ( ...[more]

PMID: 36613998

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Project description:Potassium (K(+)) channels are specialized membrane proteins that are able to facilitate and regulate the conduction of K(+) through cell membranes. Comprising five specific cation binding sites (S(0)-S(4)) formed by the backbone carbonyl groups of conserved residues common to all K(+) channels, the narrow selectivity filter allows fast conduction of K(+) while being highly selective for K(+) over Na(+). To extend our knowledge of the microscopic mechanism underlying selectivity in K(+) channels, we characterize the free energy landscapes governing the entry and translocation of a Na(+) or a K(+) from the extracellular side into the selectivity filter of KcsA. The entry process of an extracellular ion is examined in the presence of two additional K(+) in the pore, and the three-ion potential of mean force is computed using extensive all-atom umbrella sampling molecular dynamics simulations. A comparison of the potentials of mean force yields a number of important results. First, the free energy minima corresponding to configurations with extracellular K(+) or Na(+) in binding site S(0) or S(1) are similar in depth, suggesting that the thermodynamic selectivity governed by the free energy minima for those two binding sites is insignificant. Second, the free energy barriers between stable multi-ion configurations are generally higher for Na(+) than for K(+), implying that the kinetics of ion conduction is slower when a Na(+) enters the pore. Third, the region corresponding to binding site S(2) near the center of the narrow pore emerges as the most selective for K(+) over Na(+). In particular, while there is a stable minimum for K(+) in site S(2), Na(+) faces a steep free energy increase with no local free energy well in this region. Lastly, analysis shows that selectivity is not correlated with the overall coordination number of the ion entering the pore, but is predominantly affected by changes in the type of coordinating ligands (carbonyls versus water molecules). These results further highlight the importance of the central region near binding site S(2) in the selectivity filter of K(+) channels.

Dataset Information

Regulation of Ion Permeation of the KcsA Channel by Applied Midinfrared Field.

Publications

Regulation of Ion Permeation of the KcsA Channel by Applied Midinfrared Field.

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