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The Malaria Secretome: From Algorithms to Essential Function in Blood Stage Infection
The malaria agent Plasmodium falciparum is predicted to export a “secretome” of several hundred proteins to remodel the host erythrocyte. Prediction of protein export is based on the presence of an ER-type signal sequence and a downstream Host-Targeting (HT) motif (which is similar to, but distinct...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408878/ https://www.ncbi.nlm.nih.gov/pubmed/18551176 http://dx.doi.org/10.1371/journal.ppat.1000084 |
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author | van Ooij, Christiaan Tamez, Pamela Bhattacharjee, Souvik Hiller, N. Luisa Harrison, Travis Liolios, Konstantinos Kooij, Taco Ramesar, Jai Balu, Bharath Adams, John Waters, Andy Janse, Chris Haldar, Kasturi |
author_facet | van Ooij, Christiaan Tamez, Pamela Bhattacharjee, Souvik Hiller, N. Luisa Harrison, Travis Liolios, Konstantinos Kooij, Taco Ramesar, Jai Balu, Bharath Adams, John Waters, Andy Janse, Chris Haldar, Kasturi |
author_sort | van Ooij, Christiaan |
collection | PubMed |
description | The malaria agent Plasmodium falciparum is predicted to export a “secretome” of several hundred proteins to remodel the host erythrocyte. Prediction of protein export is based on the presence of an ER-type signal sequence and a downstream Host-Targeting (HT) motif (which is similar to, but distinct from, the closely related Plasmodium Export Element [PEXEL]). Previous attempts to determine the entire secretome, using either the HT-motif or the PEXEL, have yielded large sets of proteins, which have not been comprehensively tested. We present here an expanded secretome that is optimized for both P. falciparum signal sequences and the HT-motif. From the most conservative of these three secretome predictions, we identify 11 proteins that are preserved across human- and rodent-infecting Plasmodium species. The conservation of these proteins likely indicates that they perform important functions in the interaction with and remodeling of the host erythrocyte important for all Plasmodium parasites. Using the piggyBac transposition system, we validate their export and find a positive prediction rate of ∼70%. Even for proteins identified by all secretomes, the positive prediction rate is not likely to exceed ∼75%. Attempted deletions of the genes encoding the conserved exported proteins were not successful, but additional functional analyses revealed the first conserved secretome function. This gave new insight into mechanisms for the assembly of the parasite-induced tubovesicular network needed for import of nutrients into the infected erythrocyte. Thus, genomic screens combined with functional assays provide unexpected and fundamental insights into host remodeling by this major human pathogen. |
format | Text |
id | pubmed-2408878 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-24088782008-06-13 The Malaria Secretome: From Algorithms to Essential Function in Blood Stage Infection van Ooij, Christiaan Tamez, Pamela Bhattacharjee, Souvik Hiller, N. Luisa Harrison, Travis Liolios, Konstantinos Kooij, Taco Ramesar, Jai Balu, Bharath Adams, John Waters, Andy Janse, Chris Haldar, Kasturi PLoS Pathog Research Article The malaria agent Plasmodium falciparum is predicted to export a “secretome” of several hundred proteins to remodel the host erythrocyte. Prediction of protein export is based on the presence of an ER-type signal sequence and a downstream Host-Targeting (HT) motif (which is similar to, but distinct from, the closely related Plasmodium Export Element [PEXEL]). Previous attempts to determine the entire secretome, using either the HT-motif or the PEXEL, have yielded large sets of proteins, which have not been comprehensively tested. We present here an expanded secretome that is optimized for both P. falciparum signal sequences and the HT-motif. From the most conservative of these three secretome predictions, we identify 11 proteins that are preserved across human- and rodent-infecting Plasmodium species. The conservation of these proteins likely indicates that they perform important functions in the interaction with and remodeling of the host erythrocyte important for all Plasmodium parasites. Using the piggyBac transposition system, we validate their export and find a positive prediction rate of ∼70%. Even for proteins identified by all secretomes, the positive prediction rate is not likely to exceed ∼75%. Attempted deletions of the genes encoding the conserved exported proteins were not successful, but additional functional analyses revealed the first conserved secretome function. This gave new insight into mechanisms for the assembly of the parasite-induced tubovesicular network needed for import of nutrients into the infected erythrocyte. Thus, genomic screens combined with functional assays provide unexpected and fundamental insights into host remodeling by this major human pathogen. Public Library of Science 2008-06-13 /pmc/articles/PMC2408878/ /pubmed/18551176 http://dx.doi.org/10.1371/journal.ppat.1000084 Text en van Ooij et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article van Ooij, Christiaan Tamez, Pamela Bhattacharjee, Souvik Hiller, N. Luisa Harrison, Travis Liolios, Konstantinos Kooij, Taco Ramesar, Jai Balu, Bharath Adams, John Waters, Andy Janse, Chris Haldar, Kasturi The Malaria Secretome: From Algorithms to Essential Function in Blood Stage Infection |
title | The Malaria Secretome: From Algorithms to Essential Function in Blood Stage Infection |
title_full | The Malaria Secretome: From Algorithms to Essential Function in Blood Stage Infection |
title_fullStr | The Malaria Secretome: From Algorithms to Essential Function in Blood Stage Infection |
title_full_unstemmed | The Malaria Secretome: From Algorithms to Essential Function in Blood Stage Infection |
title_short | The Malaria Secretome: From Algorithms to Essential Function in Blood Stage Infection |
title_sort | malaria secretome: from algorithms to essential function in blood stage infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408878/ https://www.ncbi.nlm.nih.gov/pubmed/18551176 http://dx.doi.org/10.1371/journal.ppat.1000084 |
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