Artikel
A multimeric protein complex in the sexual stages of Plasmodium falciparum
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Veröffentlicht: | 29. Januar 2014 |
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Gliederung
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During their differentiation in the human host, the gametocytes of Plasmodium falciparum display a remarkable number of adhesive proteins on their surface. These include the PfCCp protein family, six secreted proteins that assemble to multimeric protein complexes (MPCs) and locate to the parasitophorous vacuole. We now identified another MPC component, the WD40 domain-repeat protein-like protein PfWLP-1, which is expressed in gametocytes and here interacts with selected PfCCp proteins. WD40 domains are highly abundant in eukaryotic proteomes and posses a general scaffolding function by mediating protein-protein interactions. We hypothesize that PfWLP1 is involved in the assembly and folding of the PfCCp-based MPCs. We further show that the MPC is linked to the gametocyte surface via the protein interaction of PfCCp4 with Pfs230, which then binds to the GPI-anchored Pfs48/45. Lack of Pfs230 in gene-disruptant parasites results in a destabilization of the parasitophorous vacuolar space in the gametocytes. Previous studies showed that Pfs230 is cleaved at its N-terminal end, once the gametocytes are taken up by the blood-feeding mosquito and gametogenesis is initiated in the mosquito midgut. We demonstrate that Pfs230 processing results in its increased interaction with the MPC components, and impaired Pfs230 processing causes the partial release of the PfCCp proteins from the macrogamete surface. Furthermore, the GPI-anchored Pfs25 locates to the macrogamete surface during gametogenesis, and here also interacts with MPC components. While Pfs25 stays on the surface following zygote formation, the other MPC proteins disappear from the zygote surface within 3 h post-feeding. Noteworthy, several PfCCp proteins can subsequently be detected in intracellular condensed structures during ookinete formation. These structures might resemble the recently identified crystalloids, cell structures that function as protein repositories.