Domain organization of murine mdr1b P-glycoprotein: The cytoplasmic linker region is a potential dimerization domain

Shailaja Rao Juvvadi, Joseph S. Glavy, Susan Band Horwitz, George A. Orr

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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 (K(D)) 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.

Original languageEnglish (US)
Pages (from-to)442-447
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume230
Issue number2
DOIs
StatePublished - Jan 13 1997

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Domain organization of murine mdr1b P-glycoprotein: The cytoplasmic linker region is a potential dimerization domain'. Together they form a unique fingerprint.

  • Cite this