Moreau Catherine A, Bhargav Saligram P, Kumar Hirdesh, Quadt Katharina A, Piirainen Henni, Strauss Léanne, Kehrer Jessica, Streichfuss Martin, Spatz Joachim P, Wade Rebecca C, Kursula Inari, Frischknecht Friedrich
Integrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Heidelberg, Germany.
Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
PLoS Pathog. 2017 May 26;13(5):e1006412. doi: 10.1371/journal.ppat.1006412. eCollection 2017 May.
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.
肌动蛋白单体结合蛋白（肌动蛋白结合蛋白）为肌动蛋白丝的形成提供ATP - 肌动蛋白。与具有大型丝状肌动蛋白结构的高等真核细胞不同，顶复门寄生虫通常仅含有短且高度动态的微丝。在顶复门寄生虫中，肌动蛋白结合蛋白似乎是主要的单体隔离蛋白。与经典的肌动蛋白结合蛋白相比，顶复门寄生虫的肌动蛋白结合蛋白含有一个额外的臂状β - 发夹基序，我们在此表明该基序在肌动蛋白结合中起关键作用。通过使用两种肌动蛋白结合蛋白突变体进行比较分析，我们发现该基序与伯氏疟原虫子孢子的滑行运动有关，伯氏疟原虫子孢子是由蚊子传播的啮齿类疟原虫的快速迁移形式。对迁移子孢子的力测量和分子动力学模拟表明，肌动蛋白与肌动蛋白结合蛋白之间的相互作用微调了滑行运动。我们的数据表明，实现高效高速滑行的进化压力导致了这些寄生虫中独特的肌动蛋白结合蛋白 - 肌动蛋白界面。
