IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32271-7.html
   My bibliography  Save this article

Maturation and substrate processing topography of the Plasmodium falciparum invasion/egress protease plasmepsin X

Author

Listed:
  • Sumit Mukherjee

    (Washington University School of Medicine)

  • Suong Nguyen

    (Washington University School of Medicine)

  • Eashan Sharma

    (Washington University School of Medicine)

  • Daniel E. Goldberg

    (Washington University School of Medicine)

Abstract

The malaria parasite Plasmodium invades a host erythrocyte, multiplies within a parasitophorous vacuole (PV) and then ruptures the PV and erythrocyte membranes in a process known as egress. Both egress and invasion are controlled by effector proteins discharged from specialized secretory organelles. The aspartic protease plasmepsin X (PM X) regulates activity for many of these effectors, but it is unclear how PM X accesses its diverse substrates that reside in different organelles. PM X also autoprocesses to generate different isoforms. The function of this processing is not understood. We have mapped the self-cleavage sites and have constructed parasites with cleavage site mutations. Surprisingly, a quadruple mutant that remains full-length retains in vitro activity, is trafficked normally, and supports normal egress, invasion and parasite growth. The N-terminal half of the prodomain stays bound to the catalytic domain even after processing and is required for proper intracellular trafficking of PM X. We find that this enzyme cleaves microneme and exoneme substrates before discharge, while the rhoptry substrates that are dependent on PM X activity are cleaved after exoneme discharge into the PV. The data give insight into the temporal, spatial and biochemical control of this unusual but important aspartic protease.

Suggested Citation

  • Sumit Mukherjee & Suong Nguyen & Eashan Sharma & Daniel E. Goldberg, 2022. "Maturation and substrate processing topography of the Plasmodium falciparum invasion/egress protease plasmepsin X," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32271-7
    DOI: 10.1038/s41467-022-32271-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32271-7
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-32271-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Justin A. Boddey & Anthony N. Hodder & Svenja Günther & Paul R. Gilson & Heather Patsiouras & Eugene A. Kapp & J. Andrew Pearce & Tania F. de Koning-Ward & Richard J. Simpson & Brendan S. Crabb & Alan, 2010. "An aspartyl protease directs malaria effector proteins to the host cell," Nature, Nature, vol. 463(7281), pages 627-631, February.
    2. Eva S. Istvan & Jeremy P. Mallari & Victoria C. Corey & Neekesh V. Dharia & Garland R. Marshall & Elizabeth A. Winzeler & Daniel E. Goldberg, 2017. "Esterase mutation is a mechanism of resistance to antimalarial compounds," Nature Communications, Nature, vol. 8(1), pages 1-8, April.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Mubasher Mohammed & Alexis Dziedziech & Diego Macedo & Frederik Huppertz & Ylva Veith & Zoé Postel & Elena Christ & Richard Scheytt & Tanja Slotte & Johan Henriksson & Johan Ankarklev, 2024. "Single-cell transcriptomics reveal transcriptional programs underlying male and female cell fate during Plasmodium falciparum gametocytogenesis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Madeline G. Dans & Coralie Boulet & Gabrielle M. Watson & William Nguyen & Jerzy M. Dziekan & Cindy Evelyn & Kitsanapong Reaksudsan & Somya Mehra & Zahra Razook & Niall D. Geoghegan & Michael J. Mlodz, 2024. "Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Tony Triglia & Stephen W. Scally & Benjamin A. Seager & Michał Pasternak & Laura F. Dagley & Alan F. Cowman, 2023. "Plasmepsin X activates the PCRCR complex of Plasmodium falciparum by processing PfRh5 for erythrocyte invasion," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Sash Lopaticki & Robyn McConville & Alan John & Niall Geoghegan & Shihab Deen Mohamed & Lisa Verzier & Ryan W. J. Steel & Cindy Evelyn & Matthew T. O’Neill & Niccolay Madiedo Soler & Nichollas E. Scot, 2022. "Tryptophan C-mannosylation is critical for Plasmodium falciparum transmission," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Krittikorn Kümpornsin & Theerarat Kochakarn & Tomas Yeo & John Okombo & Madeline R. Luth & Johanna Hoshizaki & Mukul Rawat & Richard D. Pearson & Kyra A. Schindler & Sachel Mok & Heekuk Park & Anne-Ca, 2023. "Generation of a mutator parasite to drive resistome discovery in Plasmodium falciparum," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Patrick K. Tumwebaze & Melissa D. Conrad & Martin Okitwi & Stephen Orena & Oswald Byaruhanga & Thomas Katairo & Jennifer Legac & Shreeya Garg & David Giesbrecht & Sawyer R. Smith & Frida G. Ceja & Sam, 2022. "Decreased susceptibility of Plasmodium falciparum to both dihydroartemisinin and lumefantrine in northern Uganda," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32271-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.