Single-stranded DNA binding protein from human malarial parasite Plasmodium falciparum is encoded in the nucleus and targeted to the apicoplast.
Apicoplast, an essential organelle of human malaria parasite Plasmodium falciparum contains a ∼35 kb circular genome and is a possible target for therapy. Proteins required for the replication and maintenance of the apicoplast DNA are not clearly known. Here we report the presence of single-stranded DNA binding protein (SSB) in P falciparum. PfSSB is targeted to the apicoplast and it binds to apicoplast DNA. A strong ssDNA binding activity specific to SSB was also detected in P. falciparum lysate. Both the recombinant and endogenous proteins form tetramers and the homology modelling shows the presence of an oligosaccharide/oligonucleotide-binding fold responsible for ssDNA binding. Additionally, we used SSB as a tool to track the mechanism of delayed death phenomena shown by apicoplast targeted drugs ciprofloxacin and tetracycline. We find that the transport of PfSSB is severely affected during the second life cycle following drug treatment. Moreover, the translation of PfSSB protein and not the transcription of PfSSB seem to be down-regulated specifically during second life cycle although there is no considerable change in protein expression profile between drug-treated and untreated parasites. These results suggest dual control of translocation and translation of apicoplast targeted proteins behind the delayed death phenomena.
Prusty
Dhaneswar
D
Special Centre for Molecular Medicine, School of Physical Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Dar
Ashraf
A
Priya
Rashmi
R
Sharma
Atul
A
Dana
Srikanta
S
Choudhury
Nirupam Roy
NR
Rao
N Subba
NS
Dhar
Suman Kumar
SK
D000981:Antiprotozoal Agents / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D002939:Ciprofloxacin / Q000494:pharmacology; D016054:DNA, Protozoan / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology; D005816:Genetic Complementation Test; D015388:Organelles / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D040681:Structural Homology, Protein
D000981:Antiprotozoal Agents; D016054:DNA, Protozoan; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D015800:Protozoan Proteins; D002939:Ciprofloxacin