PT  - JOURNAL ARTICLE
AU  - Paul-Christian Burda
AU  - Thomas Crosskey
AU  - Katharina Lauk
AU  - Aimo Zurborg
AU  - Christoph Söhnchen
AU  - Benjamin Liffner
AU  - Louisa Wilcke
AU  - Jan Strauss
AU  - Cy Jeffries
AU  - Dmitri I. Svergun
AU  - Danny W. Wilson
AU  - Matthias Wilmanns
AU  - Tim-Wolf Gilberger
TI  - Structure-based identification and functional characterization of an essential lipocalin in the malaria parasite <em>Plasmodium falciparum</em>
AID  - 10.1101/2020.02.13.947507
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.13.947507
4099  - http://biorxiv.org/content/early/2020/02/14/2020.02.13.947507.short
4100  - http://biorxiv.org/content/early/2020/02/14/2020.02.13.947507.full
AB  - 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), the first lipocalin structurally and functionally characterized in a single-celled eukaryote. 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 red blood cells.