A single point mutation in the pore region of the epithelial Na+ channel changes ion selectivity by modifying molecular sieving.

Détails

ID Serval
serval:BIB_AF36E400FDF0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A single point mutation in the pore region of the epithelial Na+ channel changes ion selectivity by modifying molecular sieving.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Kellenberger S., Gautschi I., Schild L.
ISSN
0027-8424[print], 0027-8424[linking]
Statut éditorial
Publié
Date de publication
1999
Volume
96
Numéro
7
Pages
4170-4175
Langue
anglais
Résumé
The epithelial Na+ channel (ENaC) belongs to a new class of channel proteins called the ENaC/DEG superfamily involved in epithelial Na+ transport, mechanotransduction, and neurotransmission. The role of ENaC in Na+ homeostasis and in the control of blood pressure has been demonstrated recently by the identification of mutations in ENaC beta and gamma subunits causing hypertension. The function of ENaC in Na+ reabsorption depends critically on its ability to discriminate between Na+ and other ions like K+ or Ca2+. ENaC is virtually impermeant to K+ ions, and the molecular basis for its high ionic selectivity is largely unknown. We have identified a conserved Ser residue in the second transmembrane domain of the ENaC alpha subunit (alphaS589), which when mutated allows larger ions such as K+, Rb+, Cs+, and divalent cations to pass through the channel. The relative ion permeability of each of the alphaS589 mutants is related inversely to the ionic radius of the permeant ion, indicating that alphaS589 mutations increase the molecular cutoff of the channel by modifying the pore geometry at the selectivity filter. Proper geometry of the pore is required to tightly accommodate Na+ and Li+ ions and to exclude larger cations. We provide evidence that ENaC discriminates between cations mainly on the basis of their size and the energy of dehydration.
Mots-clé
Amino Acid Sequence, Animals, Cations, Divalent/metabolism, Cations, Monovalent/metabolism, Conserved Sequence, Epithelial Sodium Channel, Female, Macromolecular Substances, Membrane Potentials/drug effects, Membrane Potentials/physiology, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, Oocytes/drug effects, Oocytes/physiology, Point Mutation, Protein Conformation, Rats, Recombinant Proteins/drug effects, Recombinant Proteins/metabolism, Sequence Alignment, Sequence Homology, Amino Acid, Serine, Sodium Channels/chemistry, Sodium Channels/genetics, Xenopus laevis
Pubmed
Web of science
Création de la notice
24/01/2008 13:45
Dernière modification de la notice
20/08/2019 16:18
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