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Inari Kursula lab
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High-resolution structures of malaria parasite actomyosin and actin filaments

Malaria is one of the most devastating infectious diseases in the world. The parasites causing malaria move by gliding, for which force is generated by an unusual actomyosin motor. We have determined high-resolution cryo-EM structures of the parasite actomyosin and actin filaments and a lower resolution reconstructions of the myosin light chains in the complex.

actomyosin structure
Photo:
Andrea Lopez Moreno and Inari Kursula

Main content

In our article published today in the journal PLoS Pathogens, we present the first structure of the entire malaria parasite motor complex: actin 1 (PfAct1) and myosin A (PfMyoA) with its two light chains, essential light chain (ELC) and myosin light chain 1 (MLC1). We also report a high-resolution structure of filamentous PfAct1 that reveals new atomic details of the ATPase site, including a channel, which may provide an exit route for phosphate and explain why phosphate release is faster in PfAct1 compared to canonical actins. PfAct1 goes through no conformational changes upon PfMyoA binding. Our PfMyoA structure also superimposes with a recent crystal structure of PfMyoA alone and a lower-resolution cryo-EM structure of the MyoA-Act1 filament. However, there are small but important conformational changes at the interface. Our structures serve as a starting point for drug design against malaria, which is one of the most devastating infectious diseases.

Read the full article: https://doi.org/10.1371/journal.ppat.1010408