Structure-Based Identification and Functional Characterization of a Lipocalin in the Malaria Parasite Plasmodium falciparum

Proteins of the lipocalin family are known to bind small hydrophobic ligands and are involved in various physiological processes ranging from lipid transport to oxidative stress responses. The genome of the malaria parasite Plasmodium falciparum contains a single protein PF3D7_0925900 with a lipocalin signature. Using crystallography and small-angle X-ray scattering, we show that the protein has a tetrameric structure of typical lipocalin monomers; hence we name it P. falciparum lipocalin (PfLCN). We show that PfLCN is expressed in the intraerythrocytic stages of the parasite and localizes to the parasitophorous and food vacuoles. Conditional knockdown of PfLCN impairs parasite development, which can be rescued by treatment with the radical scavenger Trolox or by temporal inhibition of hemoglobin digestion. This suggests a key function of PfLCN in counteracting oxidative stress-induced cell damage during multiplication of parasites within erythrocytes. [Display omitted] •Crystal structure of the malaria parasite lipocalin•Comparative analysis of lipocalin superfamily members in alveolate genomes•Localization of PfLipocalin to the parasitophorous vacuole and food vacuole•Reverse genetics reveal PfLipocalin function in oxidative damage control Lipocalins are a structurally conserved family of proteins and are known to bind to small hydrophobic molecules. Burda et al. identify a lipocalin in the malaria parasite using structural analysis and show that it has a function in oxidative damage control that is important for parasite growth.