Calcium, pH and ATP regulation of the gelsolin superfamily of proteins

• CapG, adseverin, gelsolin and villin are members of the gelsolin family of calcium-sensitive regulators of actin filament dynamics. While they display some common characteristics in their interactions with and activities toward actin, they each possess unique features in their architectures and in their functions. We have probed their similarities and differences by determining the effects of Ca2+, pH, and ATP on their structures. Each undergoes conformational changes associated with activation at neutral pH when only a fraction of their potential Ca2+-binding sites is occupied. Gelsolin, villin and adseverin exhibit local minima in thermal stability in environments containing approximately 25 nM free Ca2+. The thermal stability of CapG steadily increases through this range of free Ca2+ concentrations. All four proteins share an ability to sequester actin monomers in the presence of micromolar free Ca2+, enhancing the depolymerization of F-actin. Acidic conditions at non-denaturing pH values induce a reduction in thermal stability of all four proteins. However, low pH only induces the exposure of the actin-binding sites for adseverin and gelsolin, in the absence of free Ca2+. Gelsolin alone is able to bind ATP, which stabilizes it against thermal denaturation.

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