A <it>Plasmodium falciparum</it> copper-binding membrane protein with copper transport motifs

<p>Abstract</p> <p>Background</p> <p>Copper is an essential catalytic co-factor for metabolically important cellular enzymes, such as cytochrome-c oxidase. Eukaryotic cells acquire copper through a copper transport protein and distribute intracellular copper using molecular chaperones. The copper chelator, neocuproine, inhibits <it>Plasmodium falciparum</it> ring-to-trophozoite transition <it>in vitro</it>, indicating a copper requirement for malaria parasite development. How the malaria parasite acquires or secretes copper still remains to be fully elucidated.</p> <p>Methods</p> <p>PlasmoDB was searched for sequences corresponding to candidate <it>P. falciparum</it> copper-requiring proteins. The amino terminal domain of a putative <it>P. falciparum</it> copper transport protein was cloned and expressed as a maltose binding fusion protein. The copper binding ability of this protein was examined. Copper transport protein-specific anti-peptide antibodies were generated in chickens and used to establish native protein localization in <it>P. falciparum</it> parasites by immunofluorescence microscopy.</p> <p>Results</p> <p>Six <it>P. falciparum</it> copper-requiring protein orthologs and a candidate <it>P. falciparum</it> copper transport protein (PF14_0369), containing characteristic copper transport protein features, were identified in PlasmoDB. The recombinant amino terminal domain of the transport protein bound reduced copper <it>in vitro</it> and within <it>Escherichia coli</it> cells during recombinant expression. Immunolocalization studies tracked the copper binding protein translocating from the erythrocyte plasma membrane in early ring stage to a parasite membrane as the parasites developed to schizonts. The protein appears to be a PEXEL-negative membrane protein.</p> <p>Conclusion</p> <p><it>Plasmodium falciparum</it> parasites express a native protein with copper transporter characteristics that binds copper <it>in vitro</it>. Localization of the protein to the erythrocyte and parasite plasma membranes could provide a mechanism for the delivery of novel anti-malarial compounds.</p>

Abstract licence: CC BY-NC-ND

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