Visualizing Temperature Mediated Activation of Gelsolin and Its Deactivation By Pip2: A Saxs Based Study

作者：Maulik D. Badmalia, Shikha Singh, Renu Garg, Ashish · 发表于：Scientific Reports · 年份：2017 · DOI：10.1038/s41598-017-04975-0 · 被引用次数：21 · 研究领域：Cellular Mechanics and Interactions、Cardiomyopathy and Myosin Studies、Force Microscopy Techniques and Applications

Abstract This is the first report describing temperature based initiation of gelsolin’s F-actin depolymerization activity, even in absence of free Ca 2+ or low pH. Small angle X-ray scattering (SAXS) and circular dichroism (CD) studies revealed that temperature in the range of 30–40 °C is capable of opening the G1 domain alone, as remaining domains are held together by the Ca 2+ -sensitive C-tail latch without any loss in the secondary structural content. Full opening of all domains of tail-less gelsolin, and retention of closed shape for G2–G6 gelsolin merely by heating, further substantiated our findings. The Ca 2+ /pH independent activity of gelsolin near physiological temperature brought out a query: whether gelsolin is always active, and if not, what might deactivate it? Earlier, PIP 2 has been reported to render gelsolin inactive with no structural insight. Reduction in shape parameters and modeling revealed that PIP 2 reverses the temperature induced extension of g1-g2 linker leading to a compact shape seen for Ca 2+ -free gelsolin. Similar results for partially activated gelsolin (by low pH or Ca 2+ ions below 0.1 μM) imply that inside cells, depolymerization, capping, and nucleation of F-actin by gelsolin is regulated by the culmination of local Ca 2+ ion concentration, pH, temperature and PIP 2 levels.