Diverse mutational pathways converge on saturable chloroquine transport via the malaria parasite’s chloroquine resistance transporter

摘要: Mutations in the chloroquine resistance transporter (PfCRT) are primary determinant of (CQ) malaria parasite Plasmodium falciparum. A number distinct PfCRT haplotypes, containing between 4 and 10 mutations, have given rise to CQ different parts world. Here we present a detailed molecular analysis mutations (and order addition) required confer transport activity upon as well kinetic characterization diverse forms PfCRT. We measured ability more than 100 variants when expressed at surface Xenopus laevis oocytes. Multiple mutational pathways led saturable via PfCRT, but these could be separated into two main lineages. Moreover, attainment full followed rigid process which had added specific avoid reductions activity. minimum sufficed for (low) activity, few four conferred The finding that all limited their capacity suggests overcome by reoptimizing dosage.