A Mechanism for Actin Filament Severing by Malaria Parasite Actin Depolymerizing Factor 1 via a Low Affinity Binding Interface

摘要: Actin depolymerizing factor (ADF)/cofilins are essential regulators of actin turnover in eukaryotic cells. These multifunctional proteins facilitate both stabilization and severing filamentous (F)-actin a concentration-dependent manner. At high concentrations ADF/cofilins bind stably to F-actin longitudinally between two adjacent protomers forming what is called decorative interaction. Low densities ADF/cofilins, contrast, result the optimal filament. To date, how these contrasting modalities achieved by same protein remains uncertain. Here, we define proximate amino acids filament malaria parasite ADF/cofilin, PfADF1 from Plasmodium falciparum. unique among being able sever but do so without stable binding. Using chemical cross-linking mass spectrometry (XL-MS) combined with structure reconstruction describe previously overlooked binding interface on targeted PfADF1. This site distinct known that defines decoration. Furthermore, total internal reflection fluorescence (TIRF) microscopy imaging single filaments confirms this novel low affinity required for severing. Exploring beyond parasites, selective blocking decoration human cofilin (HsCOF1) using cytochalasin D increases its rate. HsCOF1 may therefore also use decoration-independent Thus our data suggest second, actin-binding be universally used