Article

Nature 463, 632-636 (4 February 2010) | doi:10.1038/nature08726; Received 30 July 2009; Accepted 7 December 2009

Plasmepsin V licenses Plasmodium proteins for export into the host erythrocyte

Ilaria Russo1,2, Shalon Babbitt1,3, Vasant Muralidharan1,3, Tamira Butler1, Anna Oksman1 & Daniel E. Goldberg1

  1. Howard Hughes Medical Institute, Washington University School of Medicine, Departments of Molecular Microbiology and Medicine, St Louis, Missouri 63110, USA
  2. Present address: Department of Experimental Medicine and Biochemical Science, University of Perugia, 06126 Perugia, Italy.
  3. These authors contributed equally to this work.

Correspondence to: Daniel E. Goldberg1 Correspondence and requests for materials should be addressed to D.E.G. (Email: Goldberg@borcim.wustl.edu).

Top

During their intraerythrocytic development, malaria parasites export hundreds of proteins to remodel their host cell. Nutrient acquisition, cytoadherence and antigenic variation are among the key virulence functions effected by this erythrocyte takeover. Proteins destined for export are synthesized in the endoplasmic reticulum (ER) and cleaved at a conserved (PEXEL) motif, which allows translocation into the host cell via an ATP-driven translocon called the PTEX complex. We report that plasmepsin V, an ER aspartic protease with distant homology to the mammalian processing enzyme BACE, recognizes the PEXEL motif and cleaves it at the correct site. This enzyme is essential for parasite viability and ER residence is essential for its function. We propose that plasmepsin V is the PEXEL protease and is an attractive enzyme for antimalarial drug development.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

REVIEWS

Nature Reviews Microbiology 8 9 201009 617 621 5 1740-1526 ...

Nature Reviews Microbiology Progress (01 Sep 2010)

Plasmodium post-genomics: better the bug you know?

Nature Reviews Microbiology Review (01 May 2006)

Malaria parasite proteins that remodel the host erythrocyte

Nature Reviews Microbiology Review (01 May 2009)