Structural insights are provided into the role of gelsolin in capping after actin severing by comparing the structure of a four-subunit actin filament fragment formed after phalloidin-stabilized filamentous-actin was treated with full-length gelsolin.
Abstract
Gelsolin is a calcium-dependent actin-binding protein composed of six homologous domains (G1-G6) and regulates cytoskeletal dynamics. Here, we present the 2.89 Å cryo-EM structure of two G1-G3s bound to a four-subunit actin filament fragment formed after phalloidin-stabilized filamentous-actin (F-actin) was treated with full-length gelsolin. The two G1-G3s interact asymmetrically with opposite sides of the fragment, with three phalloidin densities resolved at the interfaces between neighboring actin subunits and bound nucleotides are observed as ADP or ADP·Pi across the fragment. Structural comparisons showed that the fragment is closer to barbed-end F-actin and internal F-actin core conformations than to monomeric actin or free pointed-end F-actin. Within the fragment, A0/A1 and A2/A3 differed in interdomain twist and W-loop gate opening, and comparisons with filament-bound gelsolin complexes indicated related but non-identical G1-G3 arrangements on the two sides. These results provide structural insights into the role of gelsolin in capping after actin severing.
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