Trimethylamine N-oxide abolishes the chaperone activity of α-casein: an intrinsically disordered protein

Abstract Osmolytes (small molecules that help in circumventing stresses) are known to promote protein folding and prevent aggregation in the case of globular proteins. However, the effect of such osmolytes on the structure and function of intrinsically disordered proteins (IDPs) has not been clearly...

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Autores principales:	Mohd Younus Bhat, Laishram Rajendrakumar Singh, Tanveer Ali Dar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/69c95b65d9854712ae27837d5124e9a6
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spelling	oai:doaj.org-article:69c95b65d9854712ae27837d5124e9a62021-12-02T15:04:52ZTrimethylamine N-oxide abolishes the chaperone activity of α-casein: an intrinsically disordered protein10.1038/s41598-017-06836-22045-2322https://doaj.org/article/69c95b65d9854712ae27837d5124e9a62017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06836-2https://doaj.org/toc/2045-2322Abstract Osmolytes (small molecules that help in circumventing stresses) are known to promote protein folding and prevent aggregation in the case of globular proteins. However, the effect of such osmolytes on the structure and function of intrinsically disordered proteins (IDPs) has not been clearly understood. Here we have investigated the effect of methylamine osmolytes on α-casein (an IDP present in mammalian milk) and discovered that TMAO (Trimethylamine-N-oxide) but not other methylamines renders α-casein functionless. We observed that the loss of chaperone activity of α-casein in presence of TMAO was due to the induction of an unstable aggregation-prone intermediate. The results indicate that different osmolytes may have different structural and functional consequences on IDPs, and therefore might have clinical implications for a large number of human diseases (e.g., amyloidosis, cancer, diabetes, and neurodegeneration) where IDPs are involved.Mohd Younus BhatLaishram Rajendrakumar SinghTanveer Ali DarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mohd Younus Bhat Laishram Rajendrakumar Singh Tanveer Ali Dar Trimethylamine N-oxide abolishes the chaperone activity of α-casein: an intrinsically disordered protein
description	Abstract Osmolytes (small molecules that help in circumventing stresses) are known to promote protein folding and prevent aggregation in the case of globular proteins. However, the effect of such osmolytes on the structure and function of intrinsically disordered proteins (IDPs) has not been clearly understood. Here we have investigated the effect of methylamine osmolytes on α-casein (an IDP present in mammalian milk) and discovered that TMAO (Trimethylamine-N-oxide) but not other methylamines renders α-casein functionless. We observed that the loss of chaperone activity of α-casein in presence of TMAO was due to the induction of an unstable aggregation-prone intermediate. The results indicate that different osmolytes may have different structural and functional consequences on IDPs, and therefore might have clinical implications for a large number of human diseases (e.g., amyloidosis, cancer, diabetes, and neurodegeneration) where IDPs are involved.
format	article
author	Mohd Younus Bhat Laishram Rajendrakumar Singh Tanveer Ali Dar
author_facet	Mohd Younus Bhat Laishram Rajendrakumar Singh Tanveer Ali Dar
author_sort	Mohd Younus Bhat
title	Trimethylamine N-oxide abolishes the chaperone activity of α-casein: an intrinsically disordered protein
title_short	Trimethylamine N-oxide abolishes the chaperone activity of α-casein: an intrinsically disordered protein
title_full	Trimethylamine N-oxide abolishes the chaperone activity of α-casein: an intrinsically disordered protein
title_fullStr	Trimethylamine N-oxide abolishes the chaperone activity of α-casein: an intrinsically disordered protein
title_full_unstemmed	Trimethylamine N-oxide abolishes the chaperone activity of α-casein: an intrinsically disordered protein
title_sort	trimethylamine n-oxide abolishes the chaperone activity of α-casein: an intrinsically disordered protein
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/69c95b65d9854712ae27837d5124e9a6
work_keys_str_mv	AT mohdyounusbhat trimethylaminenoxideabolishesthechaperoneactivityofacaseinanintrinsicallydisorderedprotein AT laishramrajendrakumarsingh trimethylaminenoxideabolishesthechaperoneactivityofacaseinanintrinsicallydisorderedprotein AT tanveeralidar trimethylaminenoxideabolishesthechaperoneactivityofacaseinanintrinsicallydisorderedprotein
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Trimethylamine N-oxide abolishes the chaperone activity of α-casein: an intrinsically disordered protein

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