Bonsai Gelsolin Survives Heat Induced Denaturation by Forming β-Amyloids which Leach Out Functional Monomer

Abstract Here, we report that minimal functional gelsolin i.e. fragment 28–161 can display F-actin depolymerizing property even after heating the protein to 80 °C. Small angle X-ray scattering (SAXS) data analysis confirmed that under Ca2+-free conditions, 28–161 associates into monomer to dimer and...

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Autores principales:	Maulik D. Badmalia, Pankaj Sharma, Shiv Pratap Singh Yadav, Shikha Singh, Neeraj Khatri, Renu Garg, Ashish
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8ad1e21c804f41dca963fbf023acebc8
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spelling	oai:doaj.org-article:8ad1e21c804f41dca963fbf023acebc82021-12-02T15:07:52ZBonsai Gelsolin Survives Heat Induced Denaturation by Forming β-Amyloids which Leach Out Functional Monomer10.1038/s41598-018-30951-32045-2322https://doaj.org/article/8ad1e21c804f41dca963fbf023acebc82018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-30951-3https://doaj.org/toc/2045-2322Abstract Here, we report that minimal functional gelsolin i.e. fragment 28–161 can display F-actin depolymerizing property even after heating the protein to 80 °C. Small angle X-ray scattering (SAXS) data analysis confirmed that under Ca2+-free conditions, 28–161 associates into monomer to dimer and tetramer, which later forms β-amyloids, but in presence of Ca2+, it forms dimers which proceed to non-characterizable aggregates. The dimeric association also explained the observed decrease in ellipticity in circular dichroism experiments with increase in temperature. Importantly, SAXS data based models correlated well with our crystal structure of dimeric state of 28–161. Characterization of higher order association by electron microscopy, Congo red and ThioflavinT staining assays further confirmed that only in absence of Ca2+ ions, heating transforms 28–161 into β-amyloids. Gel filtration and other experiments showed that β-amyloids keep leaching out the monomer, and the release rates could be enhanced by addition of L-Arg to the amyloids. F-actin depolymerization showed that addition of Ca2+ ions to released monomer initiated the depolymerization activity. Overall, we propose a way to compose a supramolecular assembly which releases functional protein in sustained manner which can be applied for varied potentially therapeutic interventions.Maulik D. BadmaliaPankaj SharmaShiv Pratap Singh YadavShikha SinghNeeraj KhatriRenu GargAshishNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-18 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maulik D. Badmalia Pankaj Sharma Shiv Pratap Singh Yadav Shikha Singh Neeraj Khatri Renu Garg Ashish Bonsai Gelsolin Survives Heat Induced Denaturation by Forming β-Amyloids which Leach Out Functional Monomer
description	Abstract Here, we report that minimal functional gelsolin i.e. fragment 28–161 can display F-actin depolymerizing property even after heating the protein to 80 °C. Small angle X-ray scattering (SAXS) data analysis confirmed that under Ca2+-free conditions, 28–161 associates into monomer to dimer and tetramer, which later forms β-amyloids, but in presence of Ca2+, it forms dimers which proceed to non-characterizable aggregates. The dimeric association also explained the observed decrease in ellipticity in circular dichroism experiments with increase in temperature. Importantly, SAXS data based models correlated well with our crystal structure of dimeric state of 28–161. Characterization of higher order association by electron microscopy, Congo red and ThioflavinT staining assays further confirmed that only in absence of Ca2+ ions, heating transforms 28–161 into β-amyloids. Gel filtration and other experiments showed that β-amyloids keep leaching out the monomer, and the release rates could be enhanced by addition of L-Arg to the amyloids. F-actin depolymerization showed that addition of Ca2+ ions to released monomer initiated the depolymerization activity. Overall, we propose a way to compose a supramolecular assembly which releases functional protein in sustained manner which can be applied for varied potentially therapeutic interventions.
format	article
author	Maulik D. Badmalia Pankaj Sharma Shiv Pratap Singh Yadav Shikha Singh Neeraj Khatri Renu Garg Ashish
author_facet	Maulik D. Badmalia Pankaj Sharma Shiv Pratap Singh Yadav Shikha Singh Neeraj Khatri Renu Garg Ashish
author_sort	Maulik D. Badmalia
title	Bonsai Gelsolin Survives Heat Induced Denaturation by Forming β-Amyloids which Leach Out Functional Monomer
title_short	Bonsai Gelsolin Survives Heat Induced Denaturation by Forming β-Amyloids which Leach Out Functional Monomer
title_full	Bonsai Gelsolin Survives Heat Induced Denaturation by Forming β-Amyloids which Leach Out Functional Monomer
title_fullStr	Bonsai Gelsolin Survives Heat Induced Denaturation by Forming β-Amyloids which Leach Out Functional Monomer
title_full_unstemmed	Bonsai Gelsolin Survives Heat Induced Denaturation by Forming β-Amyloids which Leach Out Functional Monomer
title_sort	bonsai gelsolin survives heat induced denaturation by forming β-amyloids which leach out functional monomer
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/8ad1e21c804f41dca963fbf023acebc8
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Bonsai Gelsolin Survives Heat Induced Denaturation by Forming β-Amyloids which Leach Out Functional Monomer

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