Full-length Plasmodium falciparum myosin A and essential light chain PfELC structures provide new anti-malarial targets
In: eLife, Jg. 9 (2020-10-01)
Online
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Zugriff:
Parasites from the genus Plasmodium are the causative agents of malaria. The mobility, infectivity, and ultimately pathogenesis ofPlasmodium falciparumrely 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 anti-malarials targeting both the glideosome motor and its regulatory elements.
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Full-length Plasmodium falciparum myosin A and essential light chain PfELC structures provide new anti-malarial targets
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Autor/in / Beteiligte Person: | Robert-Paganin, Julien ; Trybus, Kathleen M. ; Haase, Silvia ; Blake, Thomas ; Auguin, Daniel ; Krementsova, Elena B. ; Baum, Jake ; Robblee, James P. ; Moussaoui, Dihia ; Houdusse, Anne ; Centre National de la Recherche Scientifique (CNRS) ; Biologie Cellulaire et Cancer ; Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) ; Université Paris sciences et lettres (PSL) ; Laboratoire de Biologie des Ligneux et des Grandes Cultures (LBLGC) ; Université d'Orléans (UO)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) ; Department of Life Sciences ; Imperial College London |
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Zeitschrift: | eLife, Jg. 9 (2020-10-01) |
Veröffentlichung: | eLife Sciences Publications Ltd, 2020 |
Medientyp: | unknown |
ISSN: | 2050-084X (print) |
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