Structural and functional interaction sites between Na,K-ATPase and FXYD proteins.

Détails

ID Serval
serval:BIB_1B905C822E73
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Structural and functional interaction sites between Na,K-ATPase and FXYD proteins.
Périodique
The Journal of biological chemistry
Auteur⸱e⸱s
Li C., Grosdidier A., Crambert G., Horisberger J.D., Michielin O., Geering K.
ISSN
0021-9258
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
279
Numéro
37
Pages
38895-902
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
Several members of the FXYD protein family are tissue-specific regulators of Na,K-ATPase that produce distinct effects on its apparent K(+) and Na(+) affinity. Little is known about the interaction sites between the Na,K-ATPase alpha subunit and FXYD proteins that mediate the efficient association and/or the functional effects of FXYD proteins. In this study, we have analyzed the role of the transmembrane segment TM9 of the Na,K-ATPase alpha subunit in the structural and functional interaction with FXYD2, FXYD4, and FXYD7. Mutational analysis combined with expression in Xenopus oocytes reveals that Phe(956), Glu(960), Leu(964), and Phe(967) in TM9 of the Na,K-ATPase alpha subunit represent one face interacting with the three FXYD proteins. Leu(964) and Phe(967) contribute to the efficient association of FXYD proteins with the Na,K-ATPase alpha subunit, whereas Phe(956) and Glu(960) are essential for the transmission of the functional effect of FXYD proteins on the apparent K(+) affinity of Na,K-ATPase. The relative contribution of Phe(956) and Glu(960) to the K(+) effect differs for different FXYD proteins, probably reflecting the intrinsic differences of FXYD proteins on the apparent K(+) affinity of Na,K-ATPase. In contrast to the effect on the apparent K(+) affinity, Phe(956) and Glu(960) are not involved in the effect of FXYD2 and FXYD4 on the apparent Na(+) affinity of Na,K-ATPase. The mutational analysis is in good agreement with a docking model of the Na,K-ATPase/FXYD7 complex, which also predicts the importance of Phe(956), Glu(960), Leu(964), and Phe(967) in subunit interaction. In conclusion, by using mutational analysis and modeling, we show that TM9 of the Na,K-ATPase alpha subunit exposes one face of the helix that interacts with FXYD proteins and contributes to the stable interaction with FXYD proteins, as well as mediating the effect of FXYD proteins on the apparent K(+) affinity of Na,K-ATPase.
Mots-clé
Alanine, Amino Acid Sequence, Animals, Binding Sites, Cell Membrane, DNA Mutational Analysis, Electrophysiology, Glutamine, Leucine, Membrane Potentials, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, Mutation, Oocytes, Phenylalanine, Potassium, Precipitin Tests, Protein Binding, Protein Conformation, Protein Structure, Secondary, Protein Structure, Tertiary, Rats, Sodium-Potassium-Exchanging ATPase, Structure-Activity Relationship, Time Factors, Xenopus
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 12:22
Dernière modification de la notice
20/08/2019 13:52
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