Influence of C-terminal truncation of murine Serum amyloid A on fibril structure

Abstract Amyloid A (AA) amyloidosis is a systemic protein misfolding disease affecting humans and other vertebrates. While the protein precursor in humans and mice is the acute-phase reactant serum amyloid A (SAA) 1.1, the deposited fibrils consist mainly of C-terminally truncated SAA fragments, ter...

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Autores principales:	Matthies Rennegarbe, Inga Lenter, Angelika Schierhorn, Romy Sawilla, Christian Haupt
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b27108d49c674c0499766e0c7a5184f5
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spelling	oai:doaj.org-article:b27108d49c674c0499766e0c7a5184f52021-12-02T12:32:53ZInfluence of C-terminal truncation of murine Serum amyloid A on fibril structure10.1038/s41598-017-06419-12045-2322https://doaj.org/article/b27108d49c674c0499766e0c7a5184f52017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06419-1https://doaj.org/toc/2045-2322Abstract Amyloid A (AA) amyloidosis is a systemic protein misfolding disease affecting humans and other vertebrates. While the protein precursor in humans and mice is the acute-phase reactant serum amyloid A (SAA) 1.1, the deposited fibrils consist mainly of C-terminally truncated SAA fragments, termed AA proteins. For yet unknown reasons, phenotypic variations in the AA amyloid distribution pattern are clearly associated with specific AA proteins. Here we describe a bacterial expression system and chromatographic strategies to obtain significant amounts of C-terminally truncated fragments of murine SAA1.1 that correspond in truncation position to relevant pathological AA proteins found in humans. This enables us to investigate systematically structural features of derived fibrils. All fragments form fibrils under nearly physiological conditions that show similar morphological appearance and amyloid-like properties as evident from amyloid-specific dye binding, transmission electron microscopy and infrared spectroscopy. However, infrared spectroscopy suggests variations in the structural organization of the amyloid fibrils that might be derived from a modulating role of the C-terminus for the fibril structure. These results provide insights, which can help to get a better understanding of the molecular mechanisms underlying the different clinical phenotypes of AA amyloidosis.Matthies RennegarbeInga LenterAngelika SchierhornRomy SawillaChristian HauptNature 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 Matthies Rennegarbe Inga Lenter Angelika Schierhorn Romy Sawilla Christian Haupt Influence of C-terminal truncation of murine Serum amyloid A on fibril structure
description	Abstract Amyloid A (AA) amyloidosis is a systemic protein misfolding disease affecting humans and other vertebrates. While the protein precursor in humans and mice is the acute-phase reactant serum amyloid A (SAA) 1.1, the deposited fibrils consist mainly of C-terminally truncated SAA fragments, termed AA proteins. For yet unknown reasons, phenotypic variations in the AA amyloid distribution pattern are clearly associated with specific AA proteins. Here we describe a bacterial expression system and chromatographic strategies to obtain significant amounts of C-terminally truncated fragments of murine SAA1.1 that correspond in truncation position to relevant pathological AA proteins found in humans. This enables us to investigate systematically structural features of derived fibrils. All fragments form fibrils under nearly physiological conditions that show similar morphological appearance and amyloid-like properties as evident from amyloid-specific dye binding, transmission electron microscopy and infrared spectroscopy. However, infrared spectroscopy suggests variations in the structural organization of the amyloid fibrils that might be derived from a modulating role of the C-terminus for the fibril structure. These results provide insights, which can help to get a better understanding of the molecular mechanisms underlying the different clinical phenotypes of AA amyloidosis.
format	article
author	Matthies Rennegarbe Inga Lenter Angelika Schierhorn Romy Sawilla Christian Haupt
author_facet	Matthies Rennegarbe Inga Lenter Angelika Schierhorn Romy Sawilla Christian Haupt
author_sort	Matthies Rennegarbe
title	Influence of C-terminal truncation of murine Serum amyloid A on fibril structure
title_short	Influence of C-terminal truncation of murine Serum amyloid A on fibril structure
title_full	Influence of C-terminal truncation of murine Serum amyloid A on fibril structure
title_fullStr	Influence of C-terminal truncation of murine Serum amyloid A on fibril structure
title_full_unstemmed	Influence of C-terminal truncation of murine Serum amyloid A on fibril structure
title_sort	influence of c-terminal truncation of murine serum amyloid a on fibril structure
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b27108d49c674c0499766e0c7a5184f5
work_keys_str_mv	AT matthiesrennegarbe influenceofcterminaltruncationofmurineserumamyloidaonfibrilstructure AT ingalenter influenceofcterminaltruncationofmurineserumamyloidaonfibrilstructure AT angelikaschierhorn influenceofcterminaltruncationofmurineserumamyloidaonfibrilstructure AT romysawilla influenceofcterminaltruncationofmurineserumamyloidaonfibrilstructure AT christianhaupt influenceofcterminaltruncationofmurineserumamyloidaonfibrilstructure
_version_	1718393941058912256

Influence of C-terminal truncation of murine Serum amyloid A on fibril structure

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