Membrane topology and glycosylation of the human multidrug resistance-associated protein

Détails

ID Serval
serval:BIB_7342AF1139E6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Membrane topology and glycosylation of the human multidrug resistance-associated protein
Périodique
Journal of Biological Chemistry
Auteur(s)
Bakos  E., Hegedus  T., Hollo  Z., Welker  E., Tusnady  G. E., Zaman  G. J., Flens  M. J., Varadi  A., Sarkadi  B.
ISSN
0021-9258 (Print)
Statut éditorial
Publié
Date de publication
05/1996
Volume
271
Numéro
21
Pages
12322-6
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May 24
Résumé
The membrane topology of the human multidrug resistance-associated protein (MRP) was examined by flow cytometry phenotyping, immunoblotting, and limited proteolysis in drug-resistant human and baculovirus-infected insect cells, expressing either the glycosylated or the underglycosylated forms of this protein. Inhibition of N-linked glycosylation in human cells by tunicamycin did not inhibit the transport function or the antibody recognition of MRP, although its apparent molecular mass was reduced from 180 kDa to 150 kDa. Extracellular addition of trypsin or chymotrypsin had no effect either on the function or on the molecular mass of MRP, while in isolated membranes limited proteolysis produced three large membrane-bound fragments. These experiments and the alignment of the MRP sequence with the human cystic fibrosis transmembrane conductance regulator (CFTR) suggest that human MRP, similarly to CFTR, contains a tandem repeat of six transmembrane helices, each followed by a nucleotide binding domain, and that the C-terminal membrane-bound region is glycosylated. However, the N-terminal region of MRP contains an additional membrane-bound, glycosylated area with four or five transmembrane helices, which seems to be a characteristic feature of MRP-like ATP-binding cassette transporters.
Mots-clé
Animals Cell Membrane/metabolism Cells, Cultured Doxorubicin/pharmacology Drug Resistance, Multiple Glycosylation HL-60 Cells Humans P-Glycoprotein/chemistry/*metabolism Protein Conformation Spodoptera
Pubmed
Web of science
Création de la notice
24/01/2008 15:40
Dernière modification de la notice
03/03/2018 18:19
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