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A lipocalin mediates unidirectional haem biomineralization in malaria parasites
Discussion paper / Internet publication
 
ID 4662519
Digital Object Identifier DOI 10.1101/2020.02.18.954289
Author(s) Matz, Joachim M.; Drepper, Benjamin; Blum, Thorsten B.; van Genderen, Eric; Burrell, Alana; Martin, Peer; Stach, Thomas; Collinson, Lucy; Abrahams, Jan Pieter; Matuschewski, Kai; Blackman, Michael J.
Author(s) at UniBasel Abrahams, Jan Pieter
Year 2020
Month and day 03-25
Title A lipocalin mediates unidirectional haem biomineralization in malaria parasites
Series title bioRxiv
Publisher / Institution bioRxiv
Abstract 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.
edoc-URL https://edoc.unibas.ch/93648/
Full Text on edoc Available
 
   

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