Plasmodium falciparum: the pfmdr2 protein is not overexpressed in chloroquine-resistant isolates of the malaria parasite.
We have isolated and sequenced a full-length gene (pfmdr2) that has homology to the ABC (ATP-binding cassette)-type transport proteins which includes the mammalian P-glycoproteins, CFTR, and the protein product of the Plasmodium falciparum pfmdr1 gene. The protein encoded by the pfmdr2 gene has 10 hydrophobic domains followed by a region homologous to the nucleotide binding fold of the ABC transport proteins. The pfmdr2 protein also shows homology outside the nucleotide binding fold and some structural similarity to HMT1, a protein involved in heavy metal tolerance in Schizosaccharomyces pombe. Antibodies raised to the pfmdr2 protein react with a 110-kDa band and localization by immunofluorescence suggests that protein is expressed over the whole parasite and may be located on the plasma membrane of the parasite. Comparison of the level of expression of the pfmdr2 protein in chloroquine-resistant and -sensitive parasites show that it is present at approximately equal levels which is in contrast to previous results that determined the level of the pfmdr2 transcript. These results support the evidence that pfmdr2 is not involved in the chloroquine resistance phenotype.
Rubio
J P
JP
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
Cowman
A F
AF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000276:immunology; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D002738:Chloroquine / Q000494:pharmacology*; D003001:Cloning, Molecular; D003062:Codon / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D016054:DNA, Protozoan / Q000737:chemistry; D004351:Drug Resistance / Q000235:genetics; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D017125:Genes, Protozoan; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012568:Schizosaccharomyces / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000913:Antibodies, Protozoan; D002352:Carrier Proteins; D003062:Codon; D017931:DNA Primers; D016054:DNA, Protozoan; D008562:Membrane Glycoproteins; D002738:Chloroquine