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An aspartyl protease directs malaria effector proteins to the host cell

Author

Listed:
  • Justin A. Boddey

    (The Walter and Eliza Hall Institute of Medical Research)

  • Anthony N. Hodder

    (The Walter and Eliza Hall Institute of Medical Research)

  • Svenja Günther

    (The Walter and Eliza Hall Institute of Medical Research)

  • Paul R. Gilson

    (Macfarlane Burnet Institute for Medical Research and Public Health)

  • Heather Patsiouras

    (Joint Proteomics Facility, Ludwig Institute for Cancer Research)

  • Eugene A. Kapp

    (Joint Proteomics Facility, Ludwig Institute for Cancer Research)

  • J. Andrew Pearce

    (The Walter and Eliza Hall Institute of Medical Research)

  • Tania F. de Koning-Ward

    (Deakin University)

  • Richard J. Simpson

    (The Walter and Eliza Hall Institute of Medical Research
    Joint Proteomics Facility, Ludwig Institute for Cancer Research)

  • Brendan S. Crabb

    (Macfarlane Burnet Institute for Medical Research and Public Health)

  • Alan F. Cowman

    (The Walter and Eliza Hall Institute of Medical Research)

Abstract

Plasmodium falciparum causes the virulent form of malaria and disease manifestations are linked to growth inside infected erythrocytes. To survive and evade host responses the parasite remodels the erythrocyte by exporting several hundred effector proteins beyond the surrounding parasitophorous vacuole membrane. A feature of exported proteins is a pentameric motif (RxLxE/Q/D) that is a substrate for an unknown protease. Here we show that the protein responsible for cleavage of this motif is plasmepsin V (PMV), an aspartic acid protease located in the endoplasmic reticulum. PMV cleavage reveals the export signal (xE/Q/D) at the amino terminus of cargo proteins. Expression of an identical mature protein with xQ at the N terminus generated by signal peptidase was not exported, demonstrating that PMV activity is essential and linked with other key export events. Identification of the protease responsible for export into erythrocytes provides a novel target for therapeutic intervention against this devastating disease.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:nature:v:463:y:2010:i:7281:d:10.1038_nature08728
    DOI: 10.1038/nature08728
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    Cited by:

    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. 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.

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