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Processing of Plasmodium falciparum merozoite surface protein MSP1 activates a spectrin-binding function enabling parasite egress from RBCs

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posted on 17.07.2020 by Sujaan Das, Nadine Hertrich, Abigail J Perrin, Chrislaine Withers-Martinez, Christine R Collins, Matthew L Jones, Jean M Watermeyer, Elmar T Fobes, Stephen R Martin, Helen R Saibil, Gavin J Wright, Moritz Treeck, Christian Epp, Michael J Blackman
The malaria parasite Plasmodium falciparum replicates within erythrocytes, producing progeny merozoites that are released from infected cells via a poorly understood process called egress. The most abundant merozoite surface protein, MSP1, is synthesized as a large precursor that undergoes proteolytic maturation by the parasite protease SUB1 just prior to egress. The function of MSP1 and its processing are unknown. Here we show that SUB1-mediated processing of MSP1 is important for parasite viability. Processing modifies the secondary structure of MSP1 and activates its capacity to bind spectrin, a molecular scaffold protein that is the major component of the host erythrocyte cytoskeleton. Parasites expressing an inefficiently processed MSP1 mutant show delayed egress, and merozoites lacking surface-bound MSP1 display a severe egress defect. Our results indicate that interactions between SUB1-processed merozoite surface MSP1 and the spectrin network of the erythrocyte cytoskeleton facilitate host erythrocyte rupture to enable parasite egress.

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