An aspartyl protease directs malaria effector proteins to the host cell

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Plasmodium falciparum causes the virulent form of malaria and disease manifestations are linked to growth inside infected erythrocytes. In order 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 the protein responsible for cleavage of this motif is Plasmepsin V, an aspartic acid protease located in the endoplasmic reticulum. Plasmepsin V cleavage reveals the export signal (xE/Q/D) at the N-terminus of cargo proteins. Expression of an identical mature protein with xQ at the N-terminus generated by signal peptidase was not exported demonstrating Plasmepsin V 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.

Related collections

Most cited references 26

Record: found
Abstract: found
Article: not found

The global distribution of clinical episodes of Plasmodium falciparum malaria.

Robert W. Snow, Carlos Guerra, Abdisalan Noor … (2005)

Interest in mapping the global distribution of malaria is motivated by a need to define populations at risk for appropriate resource allocation and to provide a robust framework for evaluating its global economic impact. Comparison of older and more recent malaria maps shows how the disease has been geographically restricted, but it remains entrenched in poor areas of the world with climates suitable for transmission. Here we provide an empirical approach to estimating the number of clinical events caused by Plasmodium falciparum worldwide, by using a combination of epidemiological, geographical and demographic data. We estimate that there were 515 (range 300-660) million episodes of clinical P. falciparum malaria in 2002. These global estimates are up to 50% higher than those reported by the World Health Organization (WHO) and 200% higher for areas outside Africa, reflecting the WHO's reliance upon passive national reporting for these countries. Without an informed understanding of the cartography of malaria risk, the global extent of clinical disease caused by P. falciparum will continue to be underestimated.

0 comments Cited 682 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Discovery of gene function by expression profiling of the malaria parasite life cycle.

Karine G Le Roch, Yingyao Zhou, Peter L Blair … (2003)

The completion of the genome sequence for Plasmodium falciparum, the species responsible for most malaria human deaths, has the potential to reveal hundreds of new drug targets and proteins involved in pathogenesis. However, only approximately 35% of the genes code for proteins with an identifiable function. The absence of routine genetic tools for studying Plasmodium parasites suggests that this number is unlikely to change quickly if conventional serial methods are used to characterize encoded proteins. Here, we use a high-density oligonucleotide array to generate expression profiles of human and mosquito stages of the malaria parasite's life cycle. Genes with highly correlated levels and temporal patterns of expression were often involved in similar functions or cellular processes.

0 comments Cited 421 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Is Open Access

Comparative genomics of the neglected human malaria parasite Plasmodium vivax.

Jane M-R Carlton, John H. Adams, Joana C. Silva … (2008)

The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.

1 comments Cited 358 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-journal-id): 0410462

Journal ID (pubmed-jr-id): 6011

Journal ID (nlm-ta): Nature

Title: Nature

ISSN (Print): 0028-0836

ISSN (Electronic): 1476-4687

Publication date Nihms-submitted: 23 December 2009

Publication date (Print): 4 February 2010

Publication date PMC-release: 4 August 2010

Volume: 463

Issue: 7281

Pages: 627-631

Affiliations

[1 ] The Walter and Eliza Hall Institute of Medical Research, Melbourne 3052, Australia

[2 ] MacfarlaneBurnet Institute for Medical Research & Public Health, Melbourne 3004, Australia

[3 ] Joint Proteomics Facility, Ludwig Institute for Cancer Research, Melbourne 3050, Australia. Deakin University, Waurn Ponds, 3217, Australia

[4 ] Deakin University, Waurn Ponds, 3217, Australia

Author notes

Correspondence to: Alan Cowman, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, Victoria 3001, Australia, cowman@ 123456wehi.edu.au

Article

Manuscript ID: nihpa165706

DOI: 10.1038/nature08728

PMC ID: 2818761

PubMed ID: 20130643

SO-VID: 4794b207-549f-4cdb-96f3-3e008400bee4

License:

Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

History

Funding

Funded by: National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID

Award ID: R01 AI044008-11 ||AI

Comments

Comment on this article

scite_

Smart Citations

Citing PublicationsSupportingMentioningContrasting

View Citations

See how this article has been cited at scite.ai

scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.