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...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2017-07-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-06419-1 |
| _version_ | 1818749343321030656 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T04:02:16Z |
| format | Article |
| id | doaj.art-b27108d49c674c0499766e0c7a5184f5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:02:16Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b27108d49c674c0499766e0c7a5184f52022-12-21T21:21:40ZengNature PortfolioScientific Reports2045-23222017-07-01711810.1038/s41598-017-06419-1Influence of C-terminal truncation of murine Serum amyloid A on fibril structureMatthies Rennegarbe0Inga Lenter1Angelika Schierhorn2Romy Sawilla3Christian Haupt4Institute of Protein Biochemistry, Ulm UniversityMax Planck Research Unit for Enzymology of Protein FoldingInstitute of Biochemistry and Biotechnology, Martin-Luther-UniversityInstitute of Protein Biochemistry, Ulm UniversityInstitute of Protein Biochemistry, Ulm UniversityAbstract 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.https://doi.org/10.1038/s41598-017-06419-1 |
| spellingShingle | Matthies Rennegarbe Inga Lenter Angelika Schierhorn Romy Sawilla Christian Haupt Influence of C-terminal truncation of murine Serum amyloid A on fibril structure Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-017-06419-1 |
| work_keys_str_mv | AT matthiesrennegarbe influenceofcterminaltruncationofmurineserumamyloidaonfibrilstructure AT ingalenter influenceofcterminaltruncationofmurineserumamyloidaonfibrilstructure AT angelikaschierhorn influenceofcterminaltruncationofmurineserumamyloidaonfibrilstructure AT romysawilla influenceofcterminaltruncationofmurineserumamyloidaonfibrilstructure AT christianhaupt influenceofcterminaltruncationofmurineserumamyloidaonfibrilstructure |