Abstract
Malaria parasites retain a relict plastid (apicoplast) from a photosynthetic ancestor shared with dinoflagellate algae. The apicoplast is a useful drug target; blocking housekeeping pathways such as genome replication and translation in the organelle kills parasites and protects against malaria. The apicoplast of Plasmodium falciparum encodes 30 proteins and a suite of rRNAs and tRNAs that facilitate their expression. orf105 is a hypothetical apicoplast gene that would encode a small protein (PfOrf105) with a predicted C-terminal transmembrane domain. We produced antisera to a predicted peptide within PfOrf105. Western blot analysis confirmed expression of orf105 and immunofluorescence localised the gene product to the apicoplast. Pforf105 encodes a membrane protein that has an apparent mass of 17.5 kDa and undergoes substantial turnover during the 48-hour asexual life cycle of the parasite in blood stages. The effect of actinonin, an antimalarial with a putative impact on post-translational modification of apicoplast proteins like PfOrf105, was examined. Unlike other drugs perturbing apicoplast housekeeping that induce delayed death, actinonin kills parasites immediately and has an identical drug exposure phenotype to the isopentenyl diphosphate synthesis blocker fosmidomycin. Open reading frames of similar size to PfOrf105, which also have predicted C-terminal trans membrane domains, occur in syntenic positions in all sequenced apicoplast genomes from Phylum Apicomplexa. We therefore propose to name these genes ycf93 (hypothetical chloroplast reading frame 93) according to plastid gene nomenclature convention for conserved proteins of unknown function.
Highlights
The widely used malaria prophylactic, doxycycline, was originally developed as an antibacterial that blocks protein translation by prokaryotic ribosomes [1]
The apicoplast of the human malaria parasite Plasmodium falciparum has a small (35 kb), circular genome similar to that of most plastids; the major difference being that the apicoplast genome encodes no genes for photosynthesis [8]
PfYcf93 is an apicoplast-encoded protein orf105 is an open reading frame (366 nucleotides) located on the IR-B section of the 35 kb circular genome of the apicoplast of P. falciparum (GenBank: X95276.2) that encodes a hypothetical protein of 121 amino acids [8]
Summary
The widely used malaria prophylactic, doxycycline, was originally developed as an antibacterial that blocks protein translation by prokaryotic ribosomes [1]. Any perturbation of apicoplast housekeeping appears to kill malaria parasites [2,3]. This highlights the importance of the maintenance of the apicoplast for parasite survival. The apicoplast of the human malaria parasite Plasmodium falciparum has a small (35 kb), circular genome similar to that of most plastids; the major difference being that the apicoplast genome encodes no genes for photosynthesis [8]. Thirty putative protein-encoding genes have been identified on the P. falciparum apicoplast genome, and seven of these are hypothetical proteins (open reading frames .50 amino acids) [8]. Further information of the roles of these genes, the hypothetical ones, could be valuable in targeting apicoplasts in the battle against malaria
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
