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

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Visualizing Temperature Mediated Activation of Gelsolin and Its Deactivation By Pip2: A Saxs Based Study
 
Creator Badmalia, Maulik D.
Singh, Shikha
Garg, Renu
Ashish, .
 
Subject QR Microbiology
 
Description This is the first report describing temperature based initiation of gelsolin's F-actin depolymerization activity, even in absence of free Ca2+ 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 Ca2+-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 Ca2+/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, PIP2 has been reported to render gelsolin inactive with no structural insight. Reduction in shape parameters and modeling revealed that PIP2 reverses the temperature induced extension of g1-g2 linker leading to a compact shape seen for Ca2+-free gelsolin. Similar results for partially activated gelsolin (by low pH or Ca2+ 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 Ca2+ ion concentration, pH, temperature and PIP2 levels.
 
Publisher Nature Publishing Group
 
Date 2017
 
Type Article
PeerReviewed
 
Relation http://dx.doi.org/10.1038/s41598-017-04975-0
http://crdd.osdd.net/open/2062/
 
Identifier Badmalia, Maulik D. and Singh, Shikha and Garg, Renu and Ashish, . (2017) Visualizing Temperature Mediated Activation of Gelsolin and Its Deactivation By Pip2: A Saxs Based Study. Scientific Reports, 7 (1). ISSN 2045-2322