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Protonation of key acidic residues is critical for the K(+)-selectivity of the Na/K pump
The sodium-potassium (Na/K) pump is a P-type ATPase that generates Na(+) and K(+) concentration gradients across the cell membrane. For each ATP molecule, the pump extrudes three Na(+) and imports two K(+) by alternating between outward- and inward-facing conformations that preferentially bind K(+)...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3190665/ https://www.ncbi.nlm.nih.gov/pubmed/21909093 http://dx.doi.org/10.1038/nsmb.2113 |
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author | Yu, Haibo Ratheal, Ian Artigas, Pablo Roux, Benoît |
author_facet | Yu, Haibo Ratheal, Ian Artigas, Pablo Roux, Benoît |
author_sort | Yu, Haibo |
collection | PubMed |
description | The sodium-potassium (Na/K) pump is a P-type ATPase that generates Na(+) and K(+) concentration gradients across the cell membrane. For each ATP molecule, the pump extrudes three Na(+) and imports two K(+) by alternating between outward- and inward-facing conformations that preferentially bind K(+) or Na(+), respectively. Remarkably, the selective K(+) and Na(+) binding sites share several residues, and how the pump is able to achieve the selectivity required for the functional cycle is unclear. Here, free energy perturbation molecular dynamics (FEP/MD) simulations based on the crystal structures of the Na/K pump in a K(+)-loaded state (E2·P(i)) reveal that protonation of the high-field acidic side-chains involved in the binding sites is critical to achieve the proper K(+) selectivity. This prediction is tested with electrophysiological experiments showing that the selectivity of the E2P state for K(+) over Na(+) is affected by extracellular pH. |
format | Online Article Text |
id | pubmed-3190665 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
record_format | MEDLINE/PubMed |
spelling | pubmed-31906652012-04-01 Protonation of key acidic residues is critical for the K(+)-selectivity of the Na/K pump Yu, Haibo Ratheal, Ian Artigas, Pablo Roux, Benoît Nat Struct Mol Biol Article The sodium-potassium (Na/K) pump is a P-type ATPase that generates Na(+) and K(+) concentration gradients across the cell membrane. For each ATP molecule, the pump extrudes three Na(+) and imports two K(+) by alternating between outward- and inward-facing conformations that preferentially bind K(+) or Na(+), respectively. Remarkably, the selective K(+) and Na(+) binding sites share several residues, and how the pump is able to achieve the selectivity required for the functional cycle is unclear. Here, free energy perturbation molecular dynamics (FEP/MD) simulations based on the crystal structures of the Na/K pump in a K(+)-loaded state (E2·P(i)) reveal that protonation of the high-field acidic side-chains involved in the binding sites is critical to achieve the proper K(+) selectivity. This prediction is tested with electrophysiological experiments showing that the selectivity of the E2P state for K(+) over Na(+) is affected by extracellular pH. 2011-09-11 /pmc/articles/PMC3190665/ /pubmed/21909093 http://dx.doi.org/10.1038/nsmb.2113 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Yu, Haibo Ratheal, Ian Artigas, Pablo Roux, Benoît Protonation of key acidic residues is critical for the K(+)-selectivity of the Na/K pump |
title | Protonation of key acidic residues is critical for the K(+)-selectivity of the Na/K pump |
title_full | Protonation of key acidic residues is critical for the K(+)-selectivity of the Na/K pump |
title_fullStr | Protonation of key acidic residues is critical for the K(+)-selectivity of the Na/K pump |
title_full_unstemmed | Protonation of key acidic residues is critical for the K(+)-selectivity of the Na/K pump |
title_short | Protonation of key acidic residues is critical for the K(+)-selectivity of the Na/K pump |
title_sort | protonation of key acidic residues is critical for the k(+)-selectivity of the na/k pump |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3190665/ https://www.ncbi.nlm.nih.gov/pubmed/21909093 http://dx.doi.org/10.1038/nsmb.2113 |
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