Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites.
Malaria is caused by Plasmodium parasites, which invade and replicate in erythrocytes. For Plasmodium falciparum, the major cause of severe malaria in humans, a heterotrimeric complex comprised of the secreted parasite proteins, PfCyRPA, PfRIPR and PfRH5 is essential for erythrocyte invasion, mediat...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-06-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1007809 |
| _version_ | 1798030212660723712 |
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| author | Ellen Knuepfer Katherine E Wright Surendra Kumar Prajapati Thomas A Rawlinson Franziska Mohring Marion Koch Oliver R Lyth Steven A Howell Elizabeth Villasis Ambrosius P Snijders Robert W Moon Simon J Draper Anna Rosanas-Urgell Matthew K Higgins Jake Baum Anthony A Holder |
| author_facet | Ellen Knuepfer Katherine E Wright Surendra Kumar Prajapati Thomas A Rawlinson Franziska Mohring Marion Koch Oliver R Lyth Steven A Howell Elizabeth Villasis Ambrosius P Snijders Robert W Moon Simon J Draper Anna Rosanas-Urgell Matthew K Higgins Jake Baum Anthony A Holder |
| author_sort | Ellen Knuepfer |
| collection | DOAJ |
| description | Malaria is caused by Plasmodium parasites, which invade and replicate in erythrocytes. For Plasmodium falciparum, the major cause of severe malaria in humans, a heterotrimeric complex comprised of the secreted parasite proteins, PfCyRPA, PfRIPR and PfRH5 is essential for erythrocyte invasion, mediated by the interaction between PfRH5 and erythrocyte receptor basigin (BSG). However, whilst CyRPA and RIPR are present in most Plasmodium species, RH5 is found only in the small Laverania subgenus. Existence of a complex analogous to PfRH5-PfCyRPA-PfRIPR targeting BSG, and involvement of CyRPA and RIPR in invasion, however, has not been addressed in non-Laverania parasites. Here, we establish that unlike P. falciparum, P. knowlesi and P. vivax do not universally require BSG as a host cell invasion receptor. Although we show that both PkCyRPA and PkRIPR are essential for successful invasion of erythrocytes by P. knowlesi parasites in vitro, neither protein forms a complex with each other or with an RH5-like molecule. Instead, PkRIPR is part of a different trimeric protein complex whereas PkCyRPA appears to function without other parasite binding partners. It therefore appears that in the absence of RH5, outside of the Laverania subgenus, RIPR and CyRPA have different, independent functions crucial for parasite survival. |
| first_indexed | 2024-04-11T19:36:36Z |
| format | Article |
| id | doaj.art-bf3f93b27c2446d885488d06fde5f031 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-11T19:36:36Z |
| publishDate | 2019-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-bf3f93b27c2446d885488d06fde5f0312022-12-22T04:06:50ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742019-06-01156e100780910.1371/journal.ppat.1007809Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites.Ellen KnuepferKatherine E WrightSurendra Kumar PrajapatiThomas A RawlinsonFranziska MohringMarion KochOliver R LythSteven A HowellElizabeth VillasisAmbrosius P SnijdersRobert W MoonSimon J DraperAnna Rosanas-UrgellMatthew K HigginsJake BaumAnthony A HolderMalaria is caused by Plasmodium parasites, which invade and replicate in erythrocytes. For Plasmodium falciparum, the major cause of severe malaria in humans, a heterotrimeric complex comprised of the secreted parasite proteins, PfCyRPA, PfRIPR and PfRH5 is essential for erythrocyte invasion, mediated by the interaction between PfRH5 and erythrocyte receptor basigin (BSG). However, whilst CyRPA and RIPR are present in most Plasmodium species, RH5 is found only in the small Laverania subgenus. Existence of a complex analogous to PfRH5-PfCyRPA-PfRIPR targeting BSG, and involvement of CyRPA and RIPR in invasion, however, has not been addressed in non-Laverania parasites. Here, we establish that unlike P. falciparum, P. knowlesi and P. vivax do not universally require BSG as a host cell invasion receptor. Although we show that both PkCyRPA and PkRIPR are essential for successful invasion of erythrocytes by P. knowlesi parasites in vitro, neither protein forms a complex with each other or with an RH5-like molecule. Instead, PkRIPR is part of a different trimeric protein complex whereas PkCyRPA appears to function without other parasite binding partners. It therefore appears that in the absence of RH5, outside of the Laverania subgenus, RIPR and CyRPA have different, independent functions crucial for parasite survival.https://doi.org/10.1371/journal.ppat.1007809 |
| spellingShingle | Ellen Knuepfer Katherine E Wright Surendra Kumar Prajapati Thomas A Rawlinson Franziska Mohring Marion Koch Oliver R Lyth Steven A Howell Elizabeth Villasis Ambrosius P Snijders Robert W Moon Simon J Draper Anna Rosanas-Urgell Matthew K Higgins Jake Baum Anthony A Holder Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites. PLoS Pathogens |
| title | Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites. |
| title_full | Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites. |
| title_fullStr | Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites. |
| title_full_unstemmed | Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites. |
| title_short | Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites. |
| title_sort | divergent roles for the rh5 complex components cyrpa and ripr in human infective malaria parasites |
| url | https://doi.org/10.1371/journal.ppat.1007809 |
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