Mammalian multidrug resistance gene: Complete cDNA sequence indicates strong homology to bacterial transport proteins

Philippe Gros, James Croop, David Housman

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Abstract

The complete nucleotide and primary structure (1276 amino acids) of a full length mdr cDNA capable of conferring a complete multidrug-resistant phenotype is presented. The deduced amino acid sequence suggests that mdr is a membrane glycoprotein which includes six pairs of transmembrane domains and a cluster of potentially N-linked glycosylation sites near the amino terminus. A striking feature of the protein is an internal duplication that includes approximately 500 amino acids. Each duplicated segment includes a consensus ATP-binding site. Amino acid homology is observed between the mdr gene and a series of bacterial transport genes. This strong homology suggests that a highly conserved functional unit involved in membrane transport is present in the mdr polypeptide. We propose that an energy-dependent transport mechanism is responsible for the multidrug-resistant phenotype.

Original languageEnglish (US)
Pages (from-to)371-380
Number of pages10
JournalCell
Volume47
Issue number3
DOIs
StatePublished - Nov 7 1986

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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