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Cell Host Microbe. 2015 Oct 14;18(4):433-44. doi: 10.1016/j.chom.2015.09.007.

Processing of Plasmodium falciparum Merozoite Surface Protein MSP1 Activates a Spectrin-Binding Function Enabling Parasite Egress from RBCs.

Author information

1
The Francis Crick Institute, Mill Hill Laboratory, Mill Hill, London, NW7 1AA, UK.
2
Department für Infektiologie, Parasitologie, Universitätsklinikum Heidelberg, D-69120 Heidelberg, Germany.
3
Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH, UK.
4
Department of Crystallography, Birkbeck College, London, WC1E 7HX, UK.
5
The Francis Crick Institute, Mill Hill Laboratory, Mill Hill, London, NW7 1AA, UK; Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK. Electronic address: mike.blackman@crick.ac.uk.

Abstract

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.

PMID:
26468747
PMCID:
PMC4608996
DOI:
10.1016/j.chom.2015.09.007
[Indexed for MEDLINE]
Free PMC Article

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