Moreau CA, Bhargav SP, Kumar H, Quadt KA, Piirainen H, Strauss L, et al. (2017) A unique profilin-actin interface is important for malaria parasite motility. PLoS Pathog 13(5): e1006412. https://doi.org/10.1371/journal.ppat.1006412
A unique profilin-actin interface is important for malaria parasite motility
|Author:||Moreau, Catherine A.1; Bhargav, Saligram P.1,2; Kumar, Hirdesh1,3;|
1Integrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Heidelberg, Germany
2Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
3Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), Heidelberg, Germany
4Institute for Physical Chemistry, Biophysical Chemistry, Heidelberg University, Heidelberg, Germany
5Department of Cellular Biophysics, Max-Planck Institute for Medical Research, Heidelberg, Germany
6Center for Molecular Biology (ZMBH), DKFZ-ZMBH Alliance and Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, Heidelberg, Germany
7Department of Biomedicine, University of Bergen, Bergen, Norway
|Online Access:||PDF Full Text (PDF, 9 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe201708158115
Public Library of Science,
|Publish Date:|| 2017-08-15
Profilin is an actin monomer binding protein that provides ATP-actin for incorporation into actin filaments. In contrast to higher eukaryotic cells with their large filamentous actin structures, apicomplexan parasites typically contain only short and highly dynamic microfilaments. In apicomplexans, profilin appears to be the main monomer-sequestering protein. Compared to classical profilins, apicomplexan profilins contain an additional arm-like β-hairpin motif, which we show here to be critically involved in actin binding. Through comparative analysis using two profilin mutants, we reveal this motif to be implicated in gliding motility of Plasmodium berghei sporozoites, the rapidly migrating forms of a rodent malaria parasite transmitted by mosquitoes. Force measurements on migrating sporozoites and molecular dynamics simulations indicate that the interaction between actin and profilin fine-tunes gliding motility. Our data suggest that evolutionary pressure to achieve efficient high-speed gliding has resulted in a unique profilin-actin interface in these parasites.
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.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1183 Plant biology, microbiology, virology
For this work FF was funded by the Chica and Heinz Schaller Foundation (http://www.chs-stiftung.de) and CAM, HK, KAQ, and FF by the Human Frontier Science Program RGY0071/2011 (http://www.hfsp.org). CAM, HK, KAQ, JK, and FF were funded by the European Research Council StG 281719 (https://erc.europa.eu) and JK, HK, RCW and FF by the FRONTIER program of Heidelberg University (http://www.uni-heidelberg.de/exzellenzinitiative/zukunftskonzept/frontier_de.html). JPS, FF, LS, KAQ were funded by the Collaborative Research Center SFB 1129 of the German Research Foundation (http://www.sfb1129.de). IK was funded by the Academy of Finland grants 257537, 265112, and 292718 (http://www.aka.fi/en) and the Jane and Aatos Erkko Foundation (http://jaes.fi/en/). SPB and IK were funded by the Sigrid Jusélius foundation (http://sigridjuselius.fi/en/foundation/) and HP and IK by the Emil Aaltonen Foundation (http://www.emilaaltonen.fi). RCW was funded by the Klaus Tschira Foundation (http://www.klaus-tschira-stiftung.de).
|Academy of Finland Grant Number:||
257537 (Academy of Finland Funding decision)
265112 (Academy of Finland Funding decision)
292718 (Academy of Finland Funding decision)
Copyright: © 2017 Moreau 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.