A gating mutation in the internal pore of ASIC1a.

Détails

ID Serval
serval:BIB_5AC426092F81
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A gating mutation in the internal pore of ASIC1a.
Périodique
Journal of Biological Chemistry
Auteur(s)
Pfister Y., Gautschi I., Takeda A.N., van Bemmelen M., Kellenberger S., Schild L.
ISSN
0021-9258[print], 0021-9258[linking]
Statut éditorial
Publié
Date de publication
2006
Volume
281
Numéro
17
Pages
11787-11791
Langue
anglais
Résumé
Using a substituted cysteine accessibility scan, we have investigated the structures that form the internal pore of the acid-sensing ion channel 1a. We have identified the amino acid residues Ala-22, Ile-33, and Phe-34 in the amino terminus and Arg-43 in the first transmembrane helix, which when mutated into cysteine, were modified by intracellular application of MTSET, resulting in channel inhibition. The inhibition of the R43C mutant by internal MTSET requires opening of the channel. In addition, binding of Cd2+ ions to R43C slows the channel inactivation. This indicates that the first transmembrane helix undergoes conformational changes during channel inactivation. The effect of Cd2+ on R43C can be obtained with Cd2+ applied at either the extracellular or the intracellular side, indicating that R43C is located in the channel pore. The block of the A22C, I33C, and F34C mutants by MTSET suggests that these residues in the amino terminus of the channel also participate to the internal pore.
Mots-clé
Animals, Cadmium/metabolism, Cysteine/chemistry, Cysteine/genetics, Ion Channel Gating/physiology, Membrane Proteins/genetics, Membrane Proteins/metabolism, Microinjections, Mutagenesis, Site-Directed, Mutation/genetics, Nerve Tissue Proteins/genetics, Nerve Tissue Proteins/metabolism, Oocytes/metabolism, Patch-Clamp Techniques, Protein Conformation, Sodium Channels/genetics, Sodium Channels/metabolism, Xenopus laevis/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:45
Dernière modification de la notice
20/08/2019 15:13
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