Global identification of multiple substrates for Plasmodium falciparum SUB1, an essential malarial processing protease.


Silmon de Monerri, NC; Flynn, HR; Campos, MG; Hackett, F; Koussis, K; Withers-Martinez, C; Skehel, JM; Blackman, MJ; (2011) Global identification of multiple substrates for Plasmodium falciparum SUB1, an essential malarial processing protease. Infection and immunity, 79 (3). pp. 1086-97. ISSN 0019-9567 DOI: https://doi.org/10.1128/IAI.00902-10

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Abstract

The protozoan pathogen responsible for the most severe form of human malaria, Plasmodium falciparum, replicates asexually in erythrocytes within a membrane-bound parasitophorous vacuole (PV). Following each round of intracellular growth, the PV membrane (PVM) and host cell membrane rupture to release infectious merozoites in a protease-dependent process called egress. Previous work has shown that, just prior to egress, an essential, subtilisin-like parasite protease called PfSUB1 is discharged into the PV lumen, where it directly cleaves a number of important merozoite surface and PV proteins. These include the essential merozoite surface protein complex MSP1/6/7 and members of a family of papain-like putative proteases called SERA (serine-rich antigen) that are implicated in egress. To determine whether PfSUB1 has additional, previously unrecognized substrates, we have performed a bioinformatic and proteomic analysis of the entire late asexual blood stage proteome of the parasite. Our results demonstrate that PfSUB1 is responsible for the proteolytic processing of a range of merozoite, PV, and PVM proteins, including the rhoptry protein RAP1 (rhoptry-associated protein 1) and the merozoite surface protein MSRP2 (MSP7-related protein-2). Our findings imply multiple roles for PfSUB1 in the parasite life cycle, further supporting the case for considering the protease as a potential new antimalarial drug target.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 21220481
Web of Science ID: 287700200011
URI: http://researchonline.lshtm.ac.uk/id/eprint/1544231

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