Rubio J P, Cowman A F
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
Exp Parasitol. 1994 Sep;79(2):137-47. doi: 10.1006/expr.1994.1073.
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.
我们已经分离并测序了一个全长基因（pfmdr2），它与ABC（ATP结合盒）型转运蛋白具有同源性，这些转运蛋白包括哺乳动物的P-糖蛋白、CFTR以及恶性疟原虫pfmdr1基因的蛋白质产物。pfmdr2基因编码的蛋白质有10个疏水结构域，后面跟着一个与ABC转运蛋白核苷酸结合结构域同源的区域。pfmdr2蛋白在核苷酸结合结构域之外也显示出同源性，并且与粟酒裂殖酵母中参与重金属耐受性的蛋白质HMT1有一些结构相似性。针对pfmdr2蛋白产生的抗体与一条110 kDa的条带发生反应，免疫荧光定位表明该蛋白在整个寄生虫中表达，并且可能位于寄生虫的质膜上。对氯喹抗性和敏感寄生虫中pfmdr2蛋白表达水平的比较表明，其水平大致相等，这与之前测定pfmdr2转录本水平的结果形成对比。这些结果支持了pfmdr2不参与氯喹抗性表型的证据。
