Evidence map›Paper›PMID 37036362›Full record

ArticlemBio2023

Activation of the

Sumit Mukherjee, Armiyaw S Nasamu, Kelly C Rubiano, Daniel E Goldberg

Open access · goldAbstract read
In one paragraph

Article in mBio, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
4.9field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Frontiers in parasitology · 2026
    Article
  5. Molecular biology of the cell · 2025
    Article
  6. Comparative genomic analysis of fiveMicrobial genomics · 2025
    Article
  7. Review
  8. Article
  9. Malaria: past, present, and future.Signal transduction and targeted therapy · 2025
    Review
  10. The Plasmodium circumsporozoite protein.Trends in parasitology · 2024
    Review
  11. Review
  12. Article
  13. Profile of Daniel E. Goldberg.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  14. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Sumit Mukherjee *Division of Infectious Diseases, Department of Medicine, and Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Armiyaw S Nasamu *Division of Infectious Diseases, Department of Medicine, and Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Kelly C RubianoDivision of Infectious Diseases, Department of Medicine, and Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Daniel E GoldbergDivision of Infectious Diseases, Department of Medicine, and Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.ORCID 0000-0003-3529-8399
Washington University in St. Louis · US

Funding

Plasmepsin X function in PlasmodiumR01AI138447 · NIAID · WASHINGTON UNIVERSITY · PI GOLDBERG, DANIEL E. · 2018 to 2022
$1.9M
NIAID NIH HHS R01 AI138447
6 · The paper itself

Abstract

Following each round of replication, daughter merozoites of the malaria parasite Plasmodium falciparum escape (egress) from the infected host red blood cell (RBC) by rupturing the parasitophorous vacuole membrane (PVM) and the RBC membrane (RBCM). A proteolytic cascade orchestrated by a parasite serine protease, subtilisin-like protease 1 (SUB1), regulates the membrane breakdown. SUB1 activation involves primary autoprocessing of the 82-kDa zymogen to a 54-kDa (p54) intermediate that remains bound to its inhibitory propiece (p31) postcleavage. A second processing step converts p54 to the terminal 47-kDa (p47) form of SUB1. Although the aspartic protease plasmepsin X (PM X) has been implicated in the activation of SUB1, the mechanism remains unknown. Here, we show that upon knockdown of PM X, the inhibitory p31-p54 complex of SUB1 accumulates in the parasites. Using recombinant PM X and SUB1, we show that PM X can directly cleave both p31 and p54. We have mapped the cleavage sites on recombinant p31. Furthermore, we demonstrate that the conversion of p54 to p47 can be effected by cleavage at either SUB1 or PM X cleavage sites that are adjacent to one another. Importantly, once the p31 is removed, p54 is fully functional inside the parasites, suggesting that the conversion to p47 is dispensable for SUB1 activity. Relief of propiece inhibition via a heterologous protease is a novel mechanism for subtilisin activation.

Indexed as

MalariaMalaria, FalciparumPlasmodiumAspartic Acid EndopeptidasesErythrocytesHumansPeptide HydrolasesPlasmodium falciparumProtozoan ProteinsSubtilisinsAspartic Acid EndopeptidasesPeptide HydrolasesplasmepsinProtozoan ProteinsSubtilisinsaspartic proteaseegressmalaria

Identifiers

PMID37036362
PMCPMC10128010
OpenAlexW4363644081

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.