A Unique Profilin-Actin Interface Is Important for Malaria Parasite Motility

PLoS Pathog. 2017 May 26;13(5):e1006412. doi: 10.1371/journal.ppat.1006412. eCollection 2017 May.

Abstract

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.

MeSH terms

  • Actins / genetics
  • Actins / metabolism*
  • Animals
  • Cell Movement
  • Female
  • Humans
  • Malaria / parasitology*
  • Mice, Inbred C57BL
  • Plasmodium berghei / cytology*
  • Plasmodium berghei / genetics
  • Plasmodium berghei / growth & development
  • Plasmodium berghei / metabolism*
  • Profilins / genetics
  • Profilins / metabolism*
  • Protein Binding
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Sporozoites / cytology
  • Sporozoites / growth & development
  • Sporozoites / metabolism

Substances

  • Actins
  • Profilins
  • Protozoan Proteins

Grant support

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). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.