Membrane integration of Na,K-ATPase alpha-subunits and beta-subunit assembly

Détails

ID Serval
serval:BIB_A4A1234B8AED
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Membrane integration of Na,K-ATPase alpha-subunits and beta-subunit assembly
Périodique
Journal of Biological Chemistry
Auteur(s)
Beguin  P., Hasler  U., Beggah  A., Horisberger  J. D., Geering  K.
ISSN
0021-9258 (Print)
Statut éditorial
Publié
Date de publication
09/1998
Volume
273
Numéro
38
Pages
24921-31
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep 18
Résumé
The control of membrane insertion of polytopic proteins is still poorly understood. We carried out in vivo translation/insertion experiments in Xenopus oocytes with combined wild type or mutant membrane segments of the alpha-subunit of the heterodimeric Na, K-ATPase linked to a glycosylation reporter sequence. We confirm that the four N-terminal hydrophobic segments of the alpha-subunit behave as alternating signal anchor/stop transfer motifs necessary for two lipid-inserted membrane pairs. For the six C-terminal membrane segments, however, proper packing depends on specific sequence information and association with the beta-subunit. M5 is a very inefficient signal anchor sequence due to the presence of prolines and polar amino acids. Its correct membrane insertion is probably mediated by posttranslational hairpin formation with M6, which is favored by a proline pair in the connecting loop. M7 has partial signal anchor function, which may be mediated by the presence of glycine and glutamine residues. The formation of a transmembrane M7/M8 pair requires the association of the beta-subunit, which induces a conformational change in the connecting extracytoplasmic loop that favors M7/M8 packing. The formation of the M9/M10 pair appears to be predominantly mediated by the efficient stop transfer function of M10. Mutations that provide signal anchor function to M5, M7, and M9 abolish or impede the transport activity of the enzyme. These data illustrate the importance of specific amino acids near or within hydrophobic regions as well as of subunit oligomerization for correct topographical alignment that is necessary for proper folding and/or activity of oligomeric membrane proteins.
Mots-clé
Animals Cell Membrane/*enzymology/ultrastructure Dimerization Female Glycosylation Macromolecular Substances Models, Molecular Mutagenesis, Site-Directed Na(+)-K(+)-Exchanging ATPase/*biosynthesis/chemistry/genetics Oocytes/physiology Point Mutation Proline *Protein Structure, Secondary Recombinant Fusion Proteins/biosynthesis/chemistry Sequence Deletion Xenopus laevis
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:28
Dernière modification de la notice
08/05/2019 23:10
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