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

Abstract 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...

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Autores principales:	Maulik D. Badmalia, Shikha Singh, Renu Garg, Ashish
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b87239a562e84cf699fa14a62e788109
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spelling	oai:doaj.org-article:b87239a562e84cf699fa14a62e7881092021-12-02T12:32:26ZVisualizing Temperature Mediated Activation of Gelsolin and Its Deactivation By Pip2: A Saxs Based Study10.1038/s41598-017-04975-02045-2322https://doaj.org/article/b87239a562e84cf699fa14a62e7881092017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04975-0https://doaj.org/toc/2045-2322Abstract 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.Maulik D. BadmaliaShikha SinghRenu GargAshishNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maulik D. Badmalia Shikha Singh Renu Garg Ashish Visualizing Temperature Mediated Activation of Gelsolin and Its Deactivation By Pip2: A Saxs Based Study
description	Abstract 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.
format	article
author	Maulik D. Badmalia Shikha Singh Renu Garg Ashish
author_facet	Maulik D. Badmalia Shikha Singh Renu Garg Ashish
author_sort	Maulik D. Badmalia
title	Visualizing Temperature Mediated Activation of Gelsolin and Its Deactivation By Pip2: A Saxs Based Study
title_short	Visualizing Temperature Mediated Activation of Gelsolin and Its Deactivation By Pip2: A Saxs Based Study
title_full	Visualizing Temperature Mediated Activation of Gelsolin and Its Deactivation By Pip2: A Saxs Based Study
title_fullStr	Visualizing Temperature Mediated Activation of Gelsolin and Its Deactivation By Pip2: A Saxs Based Study
title_full_unstemmed	Visualizing Temperature Mediated Activation of Gelsolin and Its Deactivation By Pip2: A Saxs Based Study
title_sort	visualizing temperature mediated activation of gelsolin and its deactivation by pip2: a saxs based study
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b87239a562e84cf699fa14a62e788109
work_keys_str_mv	AT maulikdbadmalia visualizingtemperaturemediatedactivationofgelsolinanditsdeactivationbypip2asaxsbasedstudy AT shikhasingh visualizingtemperaturemediatedactivationofgelsolinanditsdeactivationbypip2asaxsbasedstudy AT renugarg visualizingtemperaturemediatedactivationofgelsolinanditsdeactivationbypip2asaxsbasedstudy AT ashish visualizingtemperaturemediatedactivationofgelsolinanditsdeactivationbypip2asaxsbasedstudy
_version_	1718394057850355712

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

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