The native state of prion protein (PrP) directly inhibits formation of PrP-amyloid fibrils in vitro

Abstract The conversion of globular proteins into amyloid fibrils is associated with a wide variety of human diseases. One example is the prion protein (PrP), which adopts an α-helical structure in the native state but its amyloid form is implicated in the pathogenesis of prion diseases. Previous ev...

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Autores principales:	Ryo P. Honda, Kazuo Kuwata
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8126e4635924452a844f306dd1a48911
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spelling	oai:doaj.org-article:8126e4635924452a844f306dd1a489112021-12-02T15:05:28ZThe native state of prion protein (PrP) directly inhibits formation of PrP-amyloid fibrils in vitro10.1038/s41598-017-00710-x2045-2322https://doaj.org/article/8126e4635924452a844f306dd1a489112017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00710-xhttps://doaj.org/toc/2045-2322Abstract The conversion of globular proteins into amyloid fibrils is associated with a wide variety of human diseases. One example is the prion protein (PrP), which adopts an α-helical structure in the native state but its amyloid form is implicated in the pathogenesis of prion diseases. Previous evidence has suggested that destabilization of the native state promotes amyloid formation, but the underlying mechanism remains unknown. In this study, we report that the native state of PrP serves as a potent inhibitor in the formation of PrP amyloid fibrils. By monitoring the time courses of thioflavin T fluorescence, the kinetics of amyloid formation was studied in vitro under various concentrations of pre-formed amyloid, monomer, and denaturant. Quantitative analysis of the kinetic data using various models of enzyme kinetics suggested that the native state of PrP is either an uncompetitive or noncompetitive inhibitor of amyloid formation. This study highlights the significant role of the native state in inhibiting amyloid formation, which provides new insights into the pathogenesis of misfolding diseases.Ryo P. HondaKazuo KuwataNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ryo P. Honda Kazuo Kuwata The native state of prion protein (PrP) directly inhibits formation of PrP-amyloid fibrils in vitro
description	Abstract The conversion of globular proteins into amyloid fibrils is associated with a wide variety of human diseases. One example is the prion protein (PrP), which adopts an α-helical structure in the native state but its amyloid form is implicated in the pathogenesis of prion diseases. Previous evidence has suggested that destabilization of the native state promotes amyloid formation, but the underlying mechanism remains unknown. In this study, we report that the native state of PrP serves as a potent inhibitor in the formation of PrP amyloid fibrils. By monitoring the time courses of thioflavin T fluorescence, the kinetics of amyloid formation was studied in vitro under various concentrations of pre-formed amyloid, monomer, and denaturant. Quantitative analysis of the kinetic data using various models of enzyme kinetics suggested that the native state of PrP is either an uncompetitive or noncompetitive inhibitor of amyloid formation. This study highlights the significant role of the native state in inhibiting amyloid formation, which provides new insights into the pathogenesis of misfolding diseases.
format	article
author	Ryo P. Honda Kazuo Kuwata
author_facet	Ryo P. Honda Kazuo Kuwata
author_sort	Ryo P. Honda
title	The native state of prion protein (PrP) directly inhibits formation of PrP-amyloid fibrils in vitro
title_short	The native state of prion protein (PrP) directly inhibits formation of PrP-amyloid fibrils in vitro
title_full	The native state of prion protein (PrP) directly inhibits formation of PrP-amyloid fibrils in vitro
title_fullStr	The native state of prion protein (PrP) directly inhibits formation of PrP-amyloid fibrils in vitro
title_full_unstemmed	The native state of prion protein (PrP) directly inhibits formation of PrP-amyloid fibrils in vitro
title_sort	native state of prion protein (prp) directly inhibits formation of prp-amyloid fibrils in vitro
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8126e4635924452a844f306dd1a48911
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The native state of prion protein (PrP) directly inhibits formation of PrP-amyloid fibrils in vitro

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