elife: Research reveals pathogenic mechanisms of malaria parasites.

October 15, 2020 // --- Recently, the journal eLife published new insights into the molecular mechanisms that allow malaria parasites to spread and spread disease within their hosts.
movement and infectiousness of the parasite Plasmodium falciparum, as well as its ability to eventually spread malaria in humans, depend on a large molecular complex called a glider.
new findings provide a blueprint for future antimalarial treatment designs for anti-slip movements and their regulatory elements.
parasites, including the deadliest Plasmodium falciparum, kill half of malaria each year.
as these parasites become resistant to current artemisinin-based therapies, new vaccines and preventive therapies are being vigorously developed.
climate change may increase the spread of parasite-carrying mosquitoes," said Dihia Moussaoui, the first author of the study.
, we wanted to look more deeply at the molecular mechanisms that make these parasites move between their host cells in order to identify potential new intervention targets.
the lipids in the malaria parasite has the necessary myoglobin A motor (PfMyoA), which is currently the main target of antimalarial drugs.
PfMyoA is a key molecule in the life cycle of the parasite, in part because it provides the fast motion required for the active spore-like phase of the parasite.
the molecule has a conservative spball motion domain and a lever arm that binds to the molecule's two "light chains" of PfELC and MTIP.
their study, Moussaoui and Institut Curie teamed up with the Trybus Lab at the University of Vermont to capture the first X-ray structure of the full-length PfMyoA motor in two states of Plasmodium falciparum.
their work shows that the unique start-up of the PfMyoA lever arm is generated by the interaction of specific lever arms/motion domains, allowing for greater power stroke to increase the speed of motion.
arm usually contains a sequence of amino acids called IQ-based sequences that bind to molecular light chains.
in PfMyoA, the sequence of the first IQ base sequence and the PfELC combined with it is so simple that only in recent studies is the existence of the necessary light chain realized.
Further analysis of the X-ray structure by the team showed that PfELC was essential for Plasmodium falciparum to attack red blood cells and was a weak link in the assembly of fully functional sacs, providing a new target for antimalarial disease.
the structure described here provides an accurate blueprint for designing drugs that can target PfELC binding or PfMyoA full-length motion," concludes Anne Houdusse, head of the Curie Institute.
" will reduce the function of the glial body, hinder the malaria parasite in the life cycle of the most infectious stage of movement, thereby preventing the development of disease.
.com Source: Scientists shed new light on mechanisms of malaria parasite motility Original source: Dihia Moussaoui et al, Full-length Plasmmodium falciparum myosin A and essential light light chain PfELC structures provide new anti-malarial targets, eLife (2020). DOI: 10.7554/eLife.60581.