Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export.
Malaria blood stage parasites export a large number of proteins into their host erythrocyte to change it from a container of predominantly hemoglobin optimized for the transport of oxygen into a niche for parasite propagation. To understand this process, it is crucial to know which parasite proteins...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003546&type=printable |
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| author | Arlett Heiber Florian Kruse Christian Pick Christof Grüring Sven Flemming Alexander Oberli Hanno Schoeler Silke Retzlaff Paolo Mesén-Ramírez Jan A Hiss Madhusudan Kadekoppala Leonie Hecht Anthony A Holder Tim-Wolf Gilberger Tobias Spielmann |
| author_facet | Arlett Heiber Florian Kruse Christian Pick Christof Grüring Sven Flemming Alexander Oberli Hanno Schoeler Silke Retzlaff Paolo Mesén-Ramírez Jan A Hiss Madhusudan Kadekoppala Leonie Hecht Anthony A Holder Tim-Wolf Gilberger Tobias Spielmann |
| author_sort | Arlett Heiber |
| collection | DOAJ |
| description | Malaria blood stage parasites export a large number of proteins into their host erythrocyte to change it from a container of predominantly hemoglobin optimized for the transport of oxygen into a niche for parasite propagation. To understand this process, it is crucial to know which parasite proteins are exported into the host cell. This has been aided by the PEXEL/HT sequence, a five-residue motif found in many exported proteins, leading to the prediction of the exportome. However, several PEXEL/HT negative exported proteins (PNEPs) indicate that this exportome is incomplete and it remains unknown if and how many further PNEPs exist. Here we report the identification of new PNEPs in the most virulent malaria parasite Plasmodium falciparum. This includes proteins with a domain structure deviating from previously known PNEPs and indicates that PNEPs are not a rare exception. Unexpectedly, this included members of the MSP-7 related protein (MSRP) family, suggesting unanticipated functions of MSRPs. Analyzing regions mediating export of selected new PNEPs, we show that the first 20 amino acids of PNEPs without a classical N-terminal signal peptide are sufficient to promote export of a reporter, confirming the concept that this is a shared property of all PNEPs of this type. Moreover, we took advantage of newly found soluble PNEPs to show that this type of exported protein requires unfolding to move from the parasitophorous vacuole (PV) into the host cell. This indicates that soluble PNEPs, like PEXEL/HT proteins, are exported by translocation across the PV membrane (PVM), highlighting protein translocation in the parasite periphery as a general means in protein export of malaria parasites. |
| format | Article |
| id | doaj-art-370d6bb1543042caa2ffeac0f10f68e6 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-370d6bb1543042caa2ffeac0f10f68e62025-08-20T03:46:12ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-01-0198e100354610.1371/journal.ppat.1003546Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export.Arlett HeiberFlorian KruseChristian PickChristof GrüringSven FlemmingAlexander OberliHanno SchoelerSilke RetzlaffPaolo Mesén-RamírezJan A HissMadhusudan KadekoppalaLeonie HechtAnthony A HolderTim-Wolf GilbergerTobias SpielmannMalaria blood stage parasites export a large number of proteins into their host erythrocyte to change it from a container of predominantly hemoglobin optimized for the transport of oxygen into a niche for parasite propagation. To understand this process, it is crucial to know which parasite proteins are exported into the host cell. This has been aided by the PEXEL/HT sequence, a five-residue motif found in many exported proteins, leading to the prediction of the exportome. However, several PEXEL/HT negative exported proteins (PNEPs) indicate that this exportome is incomplete and it remains unknown if and how many further PNEPs exist. Here we report the identification of new PNEPs in the most virulent malaria parasite Plasmodium falciparum. This includes proteins with a domain structure deviating from previously known PNEPs and indicates that PNEPs are not a rare exception. Unexpectedly, this included members of the MSP-7 related protein (MSRP) family, suggesting unanticipated functions of MSRPs. Analyzing regions mediating export of selected new PNEPs, we show that the first 20 amino acids of PNEPs without a classical N-terminal signal peptide are sufficient to promote export of a reporter, confirming the concept that this is a shared property of all PNEPs of this type. Moreover, we took advantage of newly found soluble PNEPs to show that this type of exported protein requires unfolding to move from the parasitophorous vacuole (PV) into the host cell. This indicates that soluble PNEPs, like PEXEL/HT proteins, are exported by translocation across the PV membrane (PVM), highlighting protein translocation in the parasite periphery as a general means in protein export of malaria parasites.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003546&type=printable |
| spellingShingle | Arlett Heiber Florian Kruse Christian Pick Christof Grüring Sven Flemming Alexander Oberli Hanno Schoeler Silke Retzlaff Paolo Mesén-Ramírez Jan A Hiss Madhusudan Kadekoppala Leonie Hecht Anthony A Holder Tim-Wolf Gilberger Tobias Spielmann Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export. PLoS Pathogens |
| title | Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export. |
| title_full | Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export. |
| title_fullStr | Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export. |
| title_full_unstemmed | Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export. |
| title_short | Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export. |
| title_sort | identification of new pneps indicates a substantial non pexel exportome and underpins common features in plasmodium falciparum protein export |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003546&type=printable |
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