A WD40-repeat protein unique to malaria parasites associates with adhesion protein complexes and is crucial for blood stage progeny
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-139728
- Background During development in human erythrocytes, Plasmodium falciparum parasites display a remarkable number of adhesive proteins on their plasma membrane. In the invasive merozoites, these include members of the PfMSP1 and PfAMA1/RON complexes, which facilitate contact between merozoites and red blood cells. In gametocytes, sexual precursor cells mediating parasite transmission to the mosquito vector, plasma membrane-associated proteins primarily belong to the PfCCp and 6-cys families with roles in fertilization. This study describes aBackground During development in human erythrocytes, Plasmodium falciparum parasites display a remarkable number of adhesive proteins on their plasma membrane. In the invasive merozoites, these include members of the PfMSP1 and PfAMA1/RON complexes, which facilitate contact between merozoites and red blood cells. In gametocytes, sexual precursor cells mediating parasite transmission to the mosquito vector, plasma membrane-associated proteins primarily belong to the PfCCp and 6-cys families with roles in fertilization. This study describes a newly identified WD40-repeat protein unique to Plasmodium species that associates with adhesion protein complexes of both merozoites and gametocytes. Methods The WD40-repeat protein-like protein PfWLP1 was identified via co-immunoprecipitation assays followed by mass spectrometry and characterized using biochemical and immunohistochemistry methods. Reverse genetics were employed for functional analysis. Results PfWLP1 is expressed both in schizonts and gametocytes. In mature schizonts, the protein localizes underneath the merozoite micronemes and interacts with PfAMA1, while in gametocytes PfWLP1 primarily accumulates underneath the plasma membrane and associates with PfCCp1 and Pfs230. Reverse genetics failed to disrupt the pfwlp1 gene, while haemagglutinin-tagging was feasible, suggesting a crucial function for PfWLP1 during blood stage replication. Conclusions This is the first report on a plasmodial WD40-repeat protein associating with cell adhesion proteins. Since WD40 domains are known to mediate protein–protein contact by serving as a rigid scaffold for protein interactions, the presented data suggest that PfWLP1 supports the stability of adhesion protein complexes of the plasmodial blood stages.…
Autor(en): | Andreas von Bohl, Andrea Kuehn, Nina Simon, Vanesa Nkwouano Ngongang, Marc Spehr, Stefan Baumeister, Jude M. Przyborski, Rainer Fischer, Gabriele Pradel |
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URN: | urn:nbn:de:bvb:20-opus-139728 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für Molekulare Infektionsbiologie |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Malaria Journal |
Erscheinungsjahr: | 2015 |
Band / Jahrgang: | 14 |
Heft / Ausgabe: | 435 |
Originalveröffentlichung / Quelle: | Malaria Journal (2015) 14:435 DOI 10.1186/s12936-015-0967-x |
DOI: | https://doi.org/10.1186/s12936-015-0967-x |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | PfAMA1; PfCCp protein; Pfs230; WD40; gametocyte; malaria; merozoite; microneme; plasmodium falciparum |
Datum der Freischaltung: | 25.10.2016 |
EU-Projektnummer / Contract (GA) number: | 223044 |
OpenAIRE: | OpenAIRE |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung |