Cargando…
Cystic Fibrosis Transmembrane Conductance Regulator: Physical Basis for Lyotropic Anion Selectivity Patterns
The cystic fibrosis transmembrane conductance regulator (CFTR) Cl channel exhibits lyotropic anion selectivity. Anions that are more readily dehydrated than Cl exhibit permeability ratios (P (S)/P (Cl)) greater than unity and also bind more tightly in the channel. We compared the selectivity of CFTR...
Autores principales: | , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
1999
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2230651/ https://www.ncbi.nlm.nih.gov/pubmed/10578016 |
_version_ | 1782150237690789888 |
---|---|
author | Smith, Stephen S. Steinle, Erich D. Meyerhoff, Mark E. Dawson, David C. |
author_facet | Smith, Stephen S. Steinle, Erich D. Meyerhoff, Mark E. Dawson, David C. |
author_sort | Smith, Stephen S. |
collection | PubMed |
description | The cystic fibrosis transmembrane conductance regulator (CFTR) Cl channel exhibits lyotropic anion selectivity. Anions that are more readily dehydrated than Cl exhibit permeability ratios (P (S)/P (Cl)) greater than unity and also bind more tightly in the channel. We compared the selectivity of CFTR to that of a synthetic anion-selective membrane [poly(vinyl chloride)–tridodecylmethylammonium chloride; PVC-TDMAC] for which the nature of the physical process that governs the anion-selective response is more readily apparent. The permeability and binding selectivity patterns of CFTR differed only by a multiplicative constant from that of the PVC-TDMAC membrane; and a continuum electrostatic model suggested that both patterns could be understood in terms of the differences in the relative stabilization of anions by water and the polarizable interior of the channel or synthetic membrane. The calculated energies of anion–channel interaction, derived from measurements of either permeability or binding, varied as a linear function of inverse ionic radius (1/r), as expected from a Born-type model of ion charging in a medium characterized by an effective dielectric constant of 19. The model predicts that large anions, like SCN, although they experience weaker interactions (relative to Cl) with water and also with the channel, are more permeant than Cl because anion–water energy is a steeper function of 1/r than is the anion–channel energy. These large anions also bind more tightly for the same reason: the reduced energy of hydration allows the net transfer energy (the well depth) to be more negative. This simple selectivity mechanism that governs permeability and binding acts to optimize the function of CFTR as a Cl filter. Anions that are smaller (more difficult to dehydrate) than Cl are energetically retarded from entering the channel, while the larger (more readily dehydrated) anions are retarded in their passage by “sticking” within the channel. |
format | Text |
id | pubmed-2230651 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1999 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22306512008-04-22 Cystic Fibrosis Transmembrane Conductance Regulator: Physical Basis for Lyotropic Anion Selectivity Patterns Smith, Stephen S. Steinle, Erich D. Meyerhoff, Mark E. Dawson, David C. J Gen Physiol Original Article The cystic fibrosis transmembrane conductance regulator (CFTR) Cl channel exhibits lyotropic anion selectivity. Anions that are more readily dehydrated than Cl exhibit permeability ratios (P (S)/P (Cl)) greater than unity and also bind more tightly in the channel. We compared the selectivity of CFTR to that of a synthetic anion-selective membrane [poly(vinyl chloride)–tridodecylmethylammonium chloride; PVC-TDMAC] for which the nature of the physical process that governs the anion-selective response is more readily apparent. The permeability and binding selectivity patterns of CFTR differed only by a multiplicative constant from that of the PVC-TDMAC membrane; and a continuum electrostatic model suggested that both patterns could be understood in terms of the differences in the relative stabilization of anions by water and the polarizable interior of the channel or synthetic membrane. The calculated energies of anion–channel interaction, derived from measurements of either permeability or binding, varied as a linear function of inverse ionic radius (1/r), as expected from a Born-type model of ion charging in a medium characterized by an effective dielectric constant of 19. The model predicts that large anions, like SCN, although they experience weaker interactions (relative to Cl) with water and also with the channel, are more permeant than Cl because anion–water energy is a steeper function of 1/r than is the anion–channel energy. These large anions also bind more tightly for the same reason: the reduced energy of hydration allows the net transfer energy (the well depth) to be more negative. This simple selectivity mechanism that governs permeability and binding acts to optimize the function of CFTR as a Cl filter. Anions that are smaller (more difficult to dehydrate) than Cl are energetically retarded from entering the channel, while the larger (more readily dehydrated) anions are retarded in their passage by “sticking” within the channel. The Rockefeller University Press 1999-12-01 /pmc/articles/PMC2230651/ /pubmed/10578016 Text en © 1999 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Original Article Smith, Stephen S. Steinle, Erich D. Meyerhoff, Mark E. Dawson, David C. Cystic Fibrosis Transmembrane Conductance Regulator: Physical Basis for Lyotropic Anion Selectivity Patterns |
title | Cystic Fibrosis Transmembrane Conductance Regulator: Physical Basis for Lyotropic Anion Selectivity Patterns |
title_full | Cystic Fibrosis Transmembrane Conductance Regulator: Physical Basis for Lyotropic Anion Selectivity Patterns |
title_fullStr | Cystic Fibrosis Transmembrane Conductance Regulator: Physical Basis for Lyotropic Anion Selectivity Patterns |
title_full_unstemmed | Cystic Fibrosis Transmembrane Conductance Regulator: Physical Basis for Lyotropic Anion Selectivity Patterns |
title_short | Cystic Fibrosis Transmembrane Conductance Regulator: Physical Basis for Lyotropic Anion Selectivity Patterns |
title_sort | cystic fibrosis transmembrane conductance regulator: physical basis for lyotropic anion selectivity patterns |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2230651/ https://www.ncbi.nlm.nih.gov/pubmed/10578016 |
work_keys_str_mv | AT smithstephens cysticfibrosistransmembraneconductanceregulatorphysicalbasisforlyotropicanionselectivitypatterns AT steinleerichd cysticfibrosistransmembraneconductanceregulatorphysicalbasisforlyotropicanionselectivitypatterns AT meyerhoffmarke cysticfibrosistransmembraneconductanceregulatorphysicalbasisforlyotropicanionselectivitypatterns AT dawsondavidc cysticfibrosistransmembraneconductanceregulatorphysicalbasisforlyotropicanionselectivitypatterns |