Abstract
The potassium channel is highly selective for K+ over Na+, and the mechanism underlying this selectivity remains unclear. We show the three-dimensional distribution functions (3D-DFs) of small cations (Li+, Na+, and K+) and the free energy profile of ions inside the open selectivity filter (SF) of the KcsA channel. Our previous results [S. Phongphanphanee, N. Yoshida, S. Oiki, F. Hirata. Abstract Book of 5th International Symposium on Molecular Science of Fluctuations toward Biological Functions, P062 (2012)] indicate that the 3D-DF for K+ exhibits distinct peaks at the sites formed by the eight carbonyl oxygen atoms belonging to the surrounding peptide-backbone and residues (the cage site). Li+ has sharp distributions in the 3D-DF at the center of a quadruplex composed of four carbonyl oxygen atoms (the plane site). Na+ has a rather diffuse distribution throughout the SF region with peaks both in the plane and in cage sites. The results provide microscopic evidence of the phenomenological findings that Li+ and Na+ are not excluded from the SF region and that the binding affinity alone does not cause the ion selectivity of KcsA. In the present study, with an ion placed explicitly along the pore axis, the free energy profiles of the ions inside the SF were calculated; from these profiles we suggest a new mechanism for selective K+ permeation. According to the model, a K+ ion must overcome a free energy barrier that is approximately half that of Na+ to exit from either of the SF mouths due to the existence of an intermediate local minimum along the route for climbing the barriers.
| Original language | English |
|---|---|
| Pages (from-to) | 97-104 |
| Number of pages | 8 |
| Journal | Pure and Applied Chemistry |
| Volume | 86 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2014 |
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All Science Journal Classification (ASJC) codes
- Chemistry(all)
- Chemical Engineering(all)
Cite this
Probing "ambivalent" snug-fit sites in the KcsA potassium channel using three-dimensional reference interaction site model (3D-RISM) theory. / Phongphanphanee, Saree; Yoshida, Norio; Oiki, Shigetoshi; Hirata, Fumio.
In: Pure and Applied Chemistry, Vol. 86, No. 2, 01.02.2014, p. 97-104.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Probing "ambivalent" snug-fit sites in the KcsA potassium channel using three-dimensional reference interaction site model (3D-RISM) theory
AU - Phongphanphanee, Saree
AU - Yoshida, Norio
AU - Oiki, Shigetoshi
AU - Hirata, Fumio
PY - 2014/2/1
Y1 - 2014/2/1
N2 - The potassium channel is highly selective for K+ over Na+, and the mechanism underlying this selectivity remains unclear. We show the three-dimensional distribution functions (3D-DFs) of small cations (Li+, Na+, and K+) and the free energy profile of ions inside the open selectivity filter (SF) of the KcsA channel. Our previous results [S. Phongphanphanee, N. Yoshida, S. Oiki, F. Hirata. Abstract Book of 5th International Symposium on Molecular Science of Fluctuations toward Biological Functions, P062 (2012)] indicate that the 3D-DF for K+ exhibits distinct peaks at the sites formed by the eight carbonyl oxygen atoms belonging to the surrounding peptide-backbone and residues (the cage site). Li+ has sharp distributions in the 3D-DF at the center of a quadruplex composed of four carbonyl oxygen atoms (the plane site). Na+ has a rather diffuse distribution throughout the SF region with peaks both in the plane and in cage sites. The results provide microscopic evidence of the phenomenological findings that Li+ and Na+ are not excluded from the SF region and that the binding affinity alone does not cause the ion selectivity of KcsA. In the present study, with an ion placed explicitly along the pore axis, the free energy profiles of the ions inside the SF were calculated; from these profiles we suggest a new mechanism for selective K+ permeation. According to the model, a K+ ion must overcome a free energy barrier that is approximately half that of Na+ to exit from either of the SF mouths due to the existence of an intermediate local minimum along the route for climbing the barriers.
AB - The potassium channel is highly selective for K+ over Na+, and the mechanism underlying this selectivity remains unclear. We show the three-dimensional distribution functions (3D-DFs) of small cations (Li+, Na+, and K+) and the free energy profile of ions inside the open selectivity filter (SF) of the KcsA channel. Our previous results [S. Phongphanphanee, N. Yoshida, S. Oiki, F. Hirata. Abstract Book of 5th International Symposium on Molecular Science of Fluctuations toward Biological Functions, P062 (2012)] indicate that the 3D-DF for K+ exhibits distinct peaks at the sites formed by the eight carbonyl oxygen atoms belonging to the surrounding peptide-backbone and residues (the cage site). Li+ has sharp distributions in the 3D-DF at the center of a quadruplex composed of four carbonyl oxygen atoms (the plane site). Na+ has a rather diffuse distribution throughout the SF region with peaks both in the plane and in cage sites. The results provide microscopic evidence of the phenomenological findings that Li+ and Na+ are not excluded from the SF region and that the binding affinity alone does not cause the ion selectivity of KcsA. In the present study, with an ion placed explicitly along the pore axis, the free energy profiles of the ions inside the SF were calculated; from these profiles we suggest a new mechanism for selective K+ permeation. According to the model, a K+ ion must overcome a free energy barrier that is approximately half that of Na+ to exit from either of the SF mouths due to the existence of an intermediate local minimum along the route for climbing the barriers.
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U2 - 10.1515/pac-2014-5018
DO - 10.1515/pac-2014-5018
M3 - Article
VL - 86
SP - 97
EP - 104
JO - Pure and Applied Chemistry
JF - Pure and Applied Chemistry
SN - 0033-4545
IS - 2
ER -