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ydaG and ydbA of Lactococcus lactis Encode a Heterodimeric ATP-binding Cassette-type Multidrug Transporter

Lubelski, J., Mazurkiewicz, P., Merkerk, R. V., Konings, W. N. & Driessen, A. J. M., 2004, In : The Journal of Biological Chemistry. 279, 33, p. 34449 - 34455 7 p.

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DOI

Multidrug resistance (MDR)-type transporters mediate the active extrusion of structurally and functionally dissimilar compounds from the cells, thereby rendering cells resistant to a range of drugs. The ydaG and ydbA genes of Lactococcus lactis encode two ATP-binding cassette half-transporters, which both share homology with MDR proteins such as LmrA from L. lactis or the mammalian P-glycoprotein. The ydaG/ydbA genes were cloned and expressed separately and jointly in L. lactis using the nisin-inducible system. When both proteins are co-expressed, several structurally dissimilar drugs such as ethidium, daunomycin, and BCECF-AM are extruded from the cell. YdaG and YdbA could be co-purified as a stable heterodimer. ATPase activity was found to be associated with the YdaG/YdbA heterodimer only and not with the individual subunits. Both the ydaG and ydbA genes are up-regulated in multidrug-resistant L. lactis strains selected for growth in the presence of a variety of toxic compounds. This is the first demonstration of a functional heterodimeric ATP-binding cassette-type MDR transporter.
Original languageEnglish
Pages (from-to)34449 - 34455
Number of pages7
JournalThe Journal of Biological Chemistry
Volume279
Issue number33
Publication statusPublished - 2004

    Keywords

  • DEPENDENT DRUG EXTRUSION, ABC-TRANSPORTERS, ESCHERICHIA-COLI, RESISTANCE PROTEIN, EFFLUX PUMPS, SYSTEMS, RECONSTITUTION, MECHANISM, LMRA, MICROORGANISMS

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