Global Shapes of F-actin Depolymerization-competent Minimal Gelsolins

• DOI: 10.1074/jbc.m113.463224
• Publication Date: 2013-08-13T00:13:13Z
• Authors: Nagesh Peddada; Amin Sagar; Yogendra S. Rathore; Vikas Choudhary; U. Bharat K. Patt...; Neeraj Khatri; Renu Garg; Ashish
• Keywords: Gelsolin; Depolymerization; Actina

Because of its ability to rapidly depolymerize F-actin, plasma gelsolin has emerged as a therapeutic molecule in different disease conditions. High amounts exogenous are, however, required treat animal models diseases. Knowing that the F-actin depolymerizing property resides N terminus, we made several truncated versions gelsolin. The smaller versions, particularly one composed first 28-161 residues, depolymerized much faster than native and other truncates at same molar ratios. Although G1-G3 loses dependence on Ca(2+) or low pH for actin depolymerization function, interestingly, G1-G2 were found regain this requirement. Small angle x-ray scattering-based shape reconstructions revealed adopts an open both presence absence well pH, whereas residues prefer collapsed states Ca(2+)-free conditions 8. mutations g2-g3 linker resulted calcium sensitivity mutant activity, although F-actin-binding sites remained exposed even Furthermore, unlike wild type G1-G3, calcium-sensitive mutants acquired closed shapes free calcium, implying role determining depolymerizing-competent condition. We demonstrate mobility G1 domain, essential depolymerization, is indirectly regulated by gelsolin-like sequence linker.