A unique profilin-actin interface is important for malaria parasite motility

Abstract:

Author summary The malaria parasite Plasmodium has two invasive forms that migrate across different tissue barriers, the ookinete and the very rapidly migrating sporozoite. Previous work has shown that the motility of these and related parasites (e.g. Toxoplasma gondii) depends on a highly dynamic actin cytoskeleton and retrograde flow of surface adhesins. These unusual actin dynamics are due to the divergent structure of protozoan actins and the actions of actin-binding proteins, which can have non-canonical functions in these parasites. Profilin is one of the most important and most investigated actin-binding proteins, which binds ADP-actin and catalyzes ADP-ATP exchange to then promote actin polymerization. Parasite profilins bind monomeric actin and contain an additional domain compared to canonical profilins. Here we show that this additional domain of profilin is critical for actin binding and rapid sporozoite motility but has little impact on the slower ookinete. Sporozoites of a parasite line carrying mutations in this domain cannot translate force production and retrograde flow into optimal parasite motility. Using molecular dynamics simulations, we find that differences between mutant parasites in their capacity to migrate can be traced back to a single hydrogen bond at the actin-profilin interface.

SEEK ID: https://publications.h-its.org/publications/271

DOI: 10.1371/journal.ppat.1006412

Research Groups: Molecular and Cellular Modeling

Publication type: Journal

Journal: PLOS Pathogens

Publisher: Public Library of Science

Citation: PLoS Pathog 13(5):e1006412

Date Published: 26th May 2017

Registered Mode: imported from a bibtex file

Authors: Catherine A. Moreau, Saligram P. Bhargav, Hirdesh Kumar, Katharina A. Quadt, Henni Piirainen, Léanne Strauss, Jessica Kehrer, Martin Streichfuss, Joachim P. Spatz, Rebecca C. Wade, Inari Kursula, Friedrich Frischknecht

Citation
Moreau, C. A., Bhargav, S. P., Kumar, H., Quadt, K. A., Piirainen, H., Strauss, L., Kehrer, J., Streichfuss, M., Spatz, J. P., Wade, R. C., Kursula, I., & Frischknecht, F. (2017). A unique profilin-actin interface is important for malaria parasite motility. In M. J. Blackman (Ed.), PLOS Pathogens (Vol. 13, Issue 5, p. e1006412). Public Library of Science (PLoS). https://doi.org/10.1371/journal.ppat.1006412
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Created: 7th Sep 2019 at 11:38

Last updated: 5th Mar 2024 at 21:23

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