A lipocalin mediates unidirectional haem biomineralization in malaria parasites

Matz, Joachim M. and Drepper, Benjamin and Blum, Thorsten B. and van Genderen, Eric and Burrell, Alana and Martin, Peer and Stach, Thomas and Collinson, Lucy and Abrahams, Jan Pieter and Matuschewski, Kai and Blackman, Michael J.. (2020) A lipocalin mediates unidirectional haem biomineralization in malaria parasites. bioRxiv.

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Official URL: https://edoc.unibas.ch/93648/

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During blood stage development, malaria parasites are challenged with the detoxification of enormous amounts of haem released during the proteolytic catabolism of erythrocytic haemoglobin. They tackle this problem by sequestering haem into bioinert crystals known as haemozoin. The mechanisms underlying this biomineralization process remain enigmatic. Here, we demonstrate that both rodent and human malaria parasite species secrete and internalize a lipocalin-like protein, PV5, to control haem crystallization. Transcriptional deregulation of PV5 in the rodent parasite Plasmodium berghei results in inordinate elongation of haemozoin crystals, while conditional PV5 inactivation in the human malaria agent Plasmodium falciparum causes excessive multi-directional crystal branching. Although haemoglobin processing remains unaffected, PV5-deficient parasites generate less haemozoin. Electron diffraction analysis indicates that despite the distinct changes in crystal morphology neither the crystalline order nor unit cell of haemozoin are affected by impaired PV5 function. Deregulation of PV5 expression renders P. berghei hypersensitive to the antimalarial drugs artesunate, chloroquine, and atovaquone, resulting in accelerated parasite clearance following drug treatment in vivo . Together, our findings demonstrate the Plasmodium -tailored role of a lipocalin family member in haemozoin formation and underscore the haem biomineralization pathway as an attractive target for therapeutic exploitation.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Nano-diffraction of Biological Specimen (Abrahams)
UniBasel Contributors:Abrahams, Jan Pieter
Item Type:Preprint
Note:Publication type according to Uni Basel Research Database: Discussion paper / Internet publication
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Last Modified:21 Feb 2023 09:51
Deposited On:21 Feb 2023 09:51

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