Structural effects and functional implications of phalloidin and jasplakinolide binding to actin filaments
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Abstract
Summary Actin undergoes structural transitions during polymerization, ATP hydrolysis and subsequent release of inorganic phosphate. Several actin binding proteins sense specific states during this transition and can thus target different regions of the actin filament. Here we show in atomic detail that phalloidin, a mushroom toxin that is routinely used to stabilize and label actin filaments, suspends the structural changes in actin, likely influencing its interaction with actin binding proteins. Furthermore, high-resolution cryo-EM structures reveal structural rearrangements in F-actin upon inorganic phosphate release in phalloidin-stabilized filaments. We find that the effect of the sponge toxin jasplakinolide differs from the one of phalloidin, despite their overlapping binding site and similar interactions with the actin filament. Analysis of structural conformations of F-actin suggests that stabilizing agents trap states within the natural conformational space of actin. Abstract Figure Highlights Five high-resolution cryo-EM structures of stabilized filamentous actin Phalloidin traps different structural states depending on when it is added The effect of phalloidin and jasplakinolide on filamentous actin is not identical Both toxins likely interfere with the binding of proteins sensing F-actin’s nucleotide state
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