Structure of Full Length Plasmodium Myosin A and its light chain PfELC, dual targets against malaria parasite pathogenesis - Archive ouverte HAL Access content directly
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Structure of Full Length Plasmodium Myosin A and its light chain PfELC, dual targets against malaria parasite pathogenesis

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Dihia Moussaoui
  • Function : Author
James P Robblee
  • Function : Author
Daniel Auguin
Elena B Krementsova
  • Function : Author
Silvia Haase
  • Function : Author
Thomas C A Blake
  • Function : Author
Jake Baum
Julien Robert-Paganin
Kathleen M Trybus
  • Function : Author
  • PersonId : 1085632
Anne Houdusse

Abstract

Parasites from the genus Plasmodium are the causative agents of malaria. The mobility, infectivity and ultimately pathogenesis of this parasite relies on a macromolecular complex, called the glideosome. At the core of the glideosome is an essential and divergent Myosin A motor (PfMyoA), a first order drug target against malaria. Here we present the full-length structure of PfMyoA in two states of its motor cycle. We report novel interactions that are essential for motor priming and the mode of recognition of its two light chains (PfELC and MTIP) by two degenerate IQ motifs. Kinetic and motility assays using PfMyoA variants, along with molecular dynamics, demonstrate how specific priming and atypical sequence adaptations tune the motor's mechano-chemical properties. Supported by evidence for an essential role of the PfELC in malaria pathogenesis, these structures provide a blueprint for the design of future antimalarials targeting both the glideosome motor and its regulatory elements.
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hal-03059369 , version 1 (12-12-2020)

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Dihia Moussaoui, James P Robblee, Daniel Auguin, Elena B Krementsova, Silvia Haase, et al.. Structure of Full Length Plasmodium Myosin A and its light chain PfELC, dual targets against malaria parasite pathogenesis. 2020. ⟨hal-03059369⟩
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