A microtubule associated protein is essential for malaria parasite transmission

Wichers, Jan Stephan; Binder, Annika M; Mesén-Ramírez, Paolo; Dorner, Lilian Patrick; Safavi, Soraya; Fuchs, Gwendolin; Lenz, Tobias; Bachmann, Anna; Wilson, Danny W.; Frischknecht, Friedrich; Gilberger, Tim‐Wolf

doi:10.1101/2022.10.18.512810

Cited by 1 publication

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“…For co-localisation experiments the plasmids p40PX-mCherry [44], pmCherry- K13_DHODH nmd3 [26], ama1 PhIL1mCherry [112] and pGRASPmCherry-BSD nmd3 [26] were used.…”

Section: Methodsmentioning

confidence: 99%

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The Kelch13 compartment is a hub of highly divergent vesicle trafficking proteins in malaria parasites

Schmidt

Wichers

Behrens

et al. 2022

Preprint

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Single amino acid changes in the parasite protein Kelch13 (K13) result in reduced susceptibility ofP. falciparumparasites to Artemisinin and its derivatives (ART). Recent work indicated that K13 and other proteins co-localising with K13 (K13 compartment proteins) are involved in the endocytic uptake of host cell cytosol (HCCU) and that a reduction in HCCU results in ART resistance. HCCU is critical for parasite survival but is poorly understood, with the K13 compartment proteins are among the few proteins so far functionally linked to this process. Here we further defined the composition of the K13 compartment by identifying four novel proteins at this site. Functional analyses, tests for ART susceptibility as well as comparisons of structural similarities using AlphaFold2 predictions of these, and previously identified proteins, showed that canonical vesicle trafficking and endocytosis domains were frequent in proteins involved in resistance and endocytosis, strengthening the link to endocytosis. Despite this, most showed unusual domain combinations and large parasite-specific regions, indicating a high level of taxon-specific adaptation. A second group of proteins did not influence endocytosis or ART resistance and was characterised by a lack of vesicle trafficking domains. We here identified the first essential protein of the second group and showed that it is needed in late-stage parasites. Overall, this work identified novel proteins functioning in endocytosis and at the K13 compartment. Together with comparisons of structural predictions it provides a repertoire of functional domains at the K13 compartment that indicate a high level of adaption of the endocytosis in malaria parasites.

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“…For co-localisation experiments the plasmids p40PX-mCherry [44], pmCherry- K13_DHODH nmd3 [26], ama1 PhIL1mCherry [112] and pGRASPmCherry-BSD nmd3 [26] were used.…”

Section: Methodsmentioning

confidence: 99%

“…All oligonucleotides used to generate DNA fragments as well as those used for genotyping PCRs are listed in table S2. For co-localisation experiments the plasmids p40PX-mCherry [44], pmCherry-K13_DHODH nmd3 [26], ama1 PhIL1mCherry [112] and pGRASPmCherry-BSD nmd3 [26] were used.…”

Section: For Generating Pfmca2mentioning

confidence: 99%