ArticleThe EMBO journal2021
Autocatalytic activation of a malarial egress protease is druggable and requires a protein cofactor.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- The inner membrane complex protein, IMC55, is dispensable for intraerythrocytic development ofMicrobiology spectrum · 2026Article
- Spatiotemporal dynamics of signal dependent exocytosis and parasitophorous vacuolar membrane rupture during Plasmodium falciparum egress.PLoS pathogens · 2026Article
- Targeting protein-protein interactions in Plasmodium: from asexual replication to sexual development.Parasites & vectors · 2026Review
- Article
- The inner membrane complex protein, IMC55, is dispensable for intra-erythrocytic development ofbioRxiv : the preprint server for biology · 2025Article
- Validated antimalarial drug target discovery using genome-scale metabolic modeling.Antimicrobial agents and chemotherapy · 2025Article
- Prodomain-driven enzyme dimerization: a pH-dependent autoinhibition mechanism that controlsmBio · 2024Article
- Enzymatic and structural characterization of HAD5, an essential phosphomannomutase of malaria-causing parasites.The Journal of biological chemistry · 2022Article
- Genetic disruption of Plasmodium falciparum Merozoite surface antigen 180 (PfMSA180) suggests an essential role during parasite egress from erythrocytes.Scientific reports · 2021Article
- Autocatalytic activation of a malarial egress protease is druggable and requires a protein cofactor.The EMBO journal · 2021Article
- Calcium in the Backstage of Malaria Parasite Biology.Frontiers in cellular and infection microbiology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Malaria parasite egress from host erythrocytes (RBCs) is regulated by discharge of a parasite serine protease called SUB1 into the parasitophorous vacuole (PV). There, SUB1 activates a PV-resident cysteine protease called SERA6, enabling host RBC rupture through SERA6-mediated degradation of the RBC cytoskeleton protein β-spectrin. Here, we show that the activation of Plasmodium falciparum SERA6 involves a second, autocatalytic step that is triggered by SUB1 cleavage. Unexpectedly, autoproteolytic maturation of SERA6 requires interaction in multimolecular complexes with a distinct PV-located protein cofactor, MSA180, that is itself a SUB1 substrate. Genetic ablation of MSA180 mimics SERA6 disruption, producing a fatal block in β-spectrin cleavage and RBC rupture. Drug-like inhibitors of SERA6 autoprocessing similarly prevent β-spectrin cleavage and egress in both P. falciparum and the emerging zoonotic pathogen P. knowlesi. Our results elucidate the egress pathway and identify SERA6 as a target for a new class of antimalarial drugs designed to prevent disease progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.