Vahokoski J, Calder LJ, Lopez AJ, Molloy JE, Kursula I, Rosenthal PB (2022) High-resolution structures of malaria parasite actomyosin and actin filaments. PLoS Pathog 18(4): e1010408. https://doi.org/10.1371/journal.ppat.1010408
High-resolution structures of malaria parasite actomyosin and actin filaments
|Author:||Vahokoski, Juha1; Calder, Lesley J.2; Lopez, Andrea J.1;|
1Department of Biomedicine, University of Bergen, Bergen, Norway
2Structural Biology of Cells and Viruses Laboratory, Francis Crick Institute, London, United Kingdom
3Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
|Online Access:||PDF Full Text (PDF, 3.6 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2022110364528
Public Library of Science,
|Publish Date:|| 2022-11-03
Malaria is responsible for half a million deaths annually and poses a huge economic burden on the developing world. The mosquito-borne parasites (Plasmodium spp.) that cause the disease depend upon an unconventional actomyosin motor for both gliding motility and host cell invasion. The motor system, often referred to as the glideosome complex, remains to be understood in molecular terms and is an attractive target for new drugs that might block the infection pathway. Here, we present the high-resolution structure of the actomyosin motor complex from Plasmodium falciparum. The complex includes the malaria parasite actin filament (PfAct1) complexed with the class XIV myosin motor (PfMyoA) and its two associated light-chains. The high-resolution core structure reveals the PfAct1:PfMyoA interface in atomic detail, while at lower-resolution, we visualize the PfMyoA light-chain binding region, including the essential light chain (PfELC) and the myosin tail interacting protein (PfMTIP). Finally, we report a bare PfAct1 filament structure at improved resolution.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This study was funded by grants from the Academy of Finland (I.K.), the Sigrid Jusélius Foundation (I.K.), and the Norwegian Research Council (I.K). P.B.R. and J.E.M. are supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001143, FC001178), the Wellcome Trust (FC001143, FC001119), and the UK Medical Research Council (FC001143, FC001119). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
All structural data related to this manuscript are available in the Protein Data Bank (PDB codes 6TU4 and 6TU7) and Electron Microscopy Data Bank (EMD-10587 and EMD-10590). The optical trapping data are included as a supplemental file (S1 Data).
© 2022 Vahokoski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.