Apicomplexan actin polymerization depends on nucleation
|Author:||Kumpula, Esa-Pekka1; Pires, Isa1; Lasiwa, Devaki1;|
1Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 7, 90220, Oulu, Finland
2Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009, Bergen, Norway
|Online Access:||PDF Full Text (PDF, 2.1 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe202103258324
|Publish Date:|| 2021-03-25
Filamentous actin is critical for apicomplexan motility and host cell invasion. Yet, parasite actin filaments are short and unstable. Their kinetic characterization has been hampered by the lack of robust quantitative methods. Using a modified labeling method, we carried out thorough biochemical characterization of malaria parasite actin. In contrast to the isodesmic polymerization mechanism suggested for Toxoplasma gondii actin, Plasmodium falciparum actin I polymerizes via the classical nucleation-elongation pathway, with kinetics similar to canonical actins. A high fragmentation rate, governed by weak lateral contacts within the filament, is likely the main reason for the short filament length. At steady state, Plasmodium actin is present in equal amounts of short filaments and dimers, with a small proportion of monomers, representing the apparent critical concentration of ~0.1 µM. The dimers polymerize but do not serve as nuclei. Our work enhances understanding of actin evolution and the mechanistic details of parasite motility, serving as a basis for exploring parasite actin and actin nucleators as drug targets against malaria and other apicomplexan parasitic diseases.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This work has been financially supported by the Academy of Finland, Sigrid Jusélius Foundation, Emil Aaltonen Foundation, and Jane and Aatos Erkko Foundation.
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