Bases of Bacterial Sodium Channel Selectivity Among Organic Cations
Hille's (1971) seminal study of organic cation selectivity of eukaryotic voltage-gated sodium channels showed a sharp size cut-off for ion permeation, such that no ion possessing a methyl group was permeant. Using the prokaryotic channel, NaChBac, we found some similarity and two peculiar diffe...
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Published in | Scientific reports Vol. 9; no. 1; pp. 15260 - 12 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
England
Nature Publishing Group
24.10.2019
Nature Publishing Group UK |
Subjects | |
Online Access | Get full text |
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Summary: | Hille's (1971) seminal study of organic cation selectivity of eukaryotic voltage-gated sodium channels showed a sharp size cut-off for ion permeation, such that no ion possessing a methyl group was permeant. Using the prokaryotic channel, NaChBac, we found some similarity and two peculiar differences in the selectivity profiles for small polyatomic cations. First, we identified a diverse group of minimally permeant cations for wildtype NaChBac, ranging in sizes from ammonium to guanidinium and tetramethylammonium; and second, for both ammonium and hydrazinium, the charge-conserving selectivity filter mutation (E191D) yielded substantial increases in relative permeability (P
/P
). The relative permeabilities varied inversely with relative K
calculated from 1D Potential of Mean Force profiles (PMFs) for the single cations traversing the channel. Several of the cations bound more strongly than Na
, and hence appear to act as blockers, as well as charge carriers. Consistent with experimental observations, the E191D mutation had little impact on Na
binding to the selectivity filter, but disrupted the binding of ammonium and hydrazinium, consequently facilitating ion permeation across the NaChBac-like filter. We concluded that for prokaryotic sodium channels, a fine balance among filter size, binding affinity, occupancy, and flexibility seems to contribute to observed functional differences. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 USDOE 89233218CNA000001 LA-UR-19-29893 |
ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-019-51605-y |