Mutations in the P-falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance
Mutations in the P-falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance
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DOI：
10.1016/s1097-2765(05)00077-8
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发表时间：
2000-10-01
期刊：
影响因子：
16
通讯作者：
Wellems, TE
中科院分区：
文献类型：
--
作者：
Fidock, DA;Nomura, T;Wellems, TE
恶性疟原虫维拉帕米可逆氯喹耐药性（CQR）的决定因素定位于7号染色体36kb片段。该片段包含一个13外显子基因pfcrt，在亚洲、非洲和南美洲的寄生虫系中具有与CQR完全相关的点突变。这些数据、转染结果和选择了一个CQR系，其中包含一个新的K761突变点，该突变点是PfCRT蛋白在CQR中的核心作用。这种跨膜蛋白定位于寄生虫的消化液泡（DV），这是Co作用的部位，其中室酸化增加与PfCRT点突变有关。PfCRT的突变可能通过对DV pH的影响导致氯喹通量的改变或药物与血素结合的减少。
The determinant of verapamil-reversible chloroquine resistance (CQR) in a Plasmodium falciparum genetic cross maps to a 36 kb segment of chromosome 7. This segment harbors a 13-exon gene, pfcrt, having point mutations that associate completely with CQR in parasite lines from Asia, Africa, and South America. These data, transfection results, and selection of a CQR line harboring a novel K761 mutation point to a central role for the PfCRT protein in CQR. This transmembrane protein localizes to the parasite digestive vacuole (DV), the site of Co action, where increased compartment acidification associates with PfCRT point mutations. Mutations in PfCRT may result in altered chloroquine flux or reduced drug binding to hematin through an effect on DV pH.