| Autor: |
Juvvadi SR; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA., Glavy JS, Horwitz SB, Orr GA |
| Jazyk: |
angličtina |
| Zdroj: |
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 1997 Jan 13; Vol. 230 (2), pp. 442-7. |
| DOI: |
10.1006/bbrc.1996.5932 |
| Abstrakt: |
P-glycoprotein is an integral membrane protein that functions as a cytotoxic drug-efflux pump. Studies suggest that the transporter exists in the membrane as a dimer and possibly higher order structures. We report the bacterial expression of the linker region (amino acids 621-688) of murine mdr1b P-glycoprotein and demonstrate that this region, which serves to link the two homologous halves of the transporter, has the potential to serve as a dimerization domain. The recombinant peptide (8742 daltons) eluted from a gel filtration column at a position corresponding to a dimer (i.e. 17,500 daltons). A dimer:monomer equilibrium, as a function of peptide concentration, was confirmed by large zone gel filtration chromatography. The dissociation constant (KD) for the dimer:monomer equilibrium was 350 nM. It was possible to dissociate the dimer by low pH (3.0) or high ionic strength (2.5 M NaCl). Dimerization was not affected by an alkaline pH of 10 or 5 mM EDTA. Studies with a truncated linker peptide indicated that the N-terminal 48 amino acids were sufficient for dimerization. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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