The Inhibition of Serum Amyloid A Protein Aggregation by a Five-Residue Peptidomimetic: Structural and Morphological Insights
Serum amyloid A (SAA) is a small protein consisting of 104 residues and, under physiological conditions, exists mainly in hexameric form. It belongs to the positive acute-phase proteins, which means that its plasma concentration increases rapidly in response to injury, inflammation, and infection. T...
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2024-10-01
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| author | Julia Witkowska Sandra Skibiszewska Paweł Wityk Marcel Pilarski Elżbieta Jankowska |
| author_facet | Julia Witkowska Sandra Skibiszewska Paweł Wityk Marcel Pilarski Elżbieta Jankowska |
| author_sort | Julia Witkowska |
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| description | Serum amyloid A (SAA) is a small protein consisting of 104 residues and, under physiological conditions, exists mainly in hexameric form. It belongs to the positive acute-phase proteins, which means that its plasma concentration increases rapidly in response to injury, inflammation, and infection. The accumulation of SAA molecules promotes the formation of amyloid aggregates, which deposit extracellularly in many organs, causing their dysfunction. In our previous work, we successfully designed a peptidomimetic that inhibited the aggregation of amyloidogenic SAA fragments. In the present paper, we show how the same inhibitor, named saa3Dip, affects the oligomerization and aggregation processes of MetSAA1.1 protein. The thioflavin T assay showed that saa3Dip inhibited its fibrillization. The measurement of the internal fluorophore fluorescence (Trp) showed differences that occurred in the tertiary structure of MetSAA1.1 in the presence of the inhibitor, which was also confirmed by CD spectra in the aromatic range. FTIR results suggested that saa3Dip could stabilize some fragments of the native structure of MetSAA1.1, which was confirmed by determining the melting temperature (Tm) of the protein–inhibitor complex. AFM images demonstrated that the presence of saa3Dip prevented the formation of large SAA aggregates. Our results suggest that saa3Dip stabilizes the native conformation of MetSAA1.1. |
| format | Article |
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| spelling | doaj-art-6bcb54c527ff41cc84c88233e329a3bd2025-08-20T02:14:16ZengMDPI AGMolecules1420-30492024-10-012921516510.3390/molecules29215165The Inhibition of Serum Amyloid A Protein Aggregation by a Five-Residue Peptidomimetic: Structural and Morphological InsightsJulia Witkowska0Sandra Skibiszewska1Paweł Wityk2Marcel Pilarski3Elżbieta Jankowska4Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, PolandFaculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, PolandFaculty of Chemistry, Gdańsk University of Technology, Narutowicza 11/12, 80-222 Gdańsk, PolandFaculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, PolandFaculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, PolandSerum amyloid A (SAA) is a small protein consisting of 104 residues and, under physiological conditions, exists mainly in hexameric form. It belongs to the positive acute-phase proteins, which means that its plasma concentration increases rapidly in response to injury, inflammation, and infection. The accumulation of SAA molecules promotes the formation of amyloid aggregates, which deposit extracellularly in many organs, causing their dysfunction. In our previous work, we successfully designed a peptidomimetic that inhibited the aggregation of amyloidogenic SAA fragments. In the present paper, we show how the same inhibitor, named saa3Dip, affects the oligomerization and aggregation processes of MetSAA1.1 protein. The thioflavin T assay showed that saa3Dip inhibited its fibrillization. The measurement of the internal fluorophore fluorescence (Trp) showed differences that occurred in the tertiary structure of MetSAA1.1 in the presence of the inhibitor, which was also confirmed by CD spectra in the aromatic range. FTIR results suggested that saa3Dip could stabilize some fragments of the native structure of MetSAA1.1, which was confirmed by determining the melting temperature (Tm) of the protein–inhibitor complex. AFM images demonstrated that the presence of saa3Dip prevented the formation of large SAA aggregates. Our results suggest that saa3Dip stabilizes the native conformation of MetSAA1.1.https://www.mdpi.com/1420-3049/29/21/5165serum amyloid Aaggregationinhibitor |
| spellingShingle | Julia Witkowska Sandra Skibiszewska Paweł Wityk Marcel Pilarski Elżbieta Jankowska The Inhibition of Serum Amyloid A Protein Aggregation by a Five-Residue Peptidomimetic: Structural and Morphological Insights Molecules serum amyloid A aggregation inhibitor |
| title | The Inhibition of Serum Amyloid A Protein Aggregation by a Five-Residue Peptidomimetic: Structural and Morphological Insights |
| title_full | The Inhibition of Serum Amyloid A Protein Aggregation by a Five-Residue Peptidomimetic: Structural and Morphological Insights |
| title_fullStr | The Inhibition of Serum Amyloid A Protein Aggregation by a Five-Residue Peptidomimetic: Structural and Morphological Insights |
| title_full_unstemmed | The Inhibition of Serum Amyloid A Protein Aggregation by a Five-Residue Peptidomimetic: Structural and Morphological Insights |
| title_short | The Inhibition of Serum Amyloid A Protein Aggregation by a Five-Residue Peptidomimetic: Structural and Morphological Insights |
| title_sort | inhibition of serum amyloid a protein aggregation by a five residue peptidomimetic structural and morphological insights |
| topic | serum amyloid A aggregation inhibitor |
| url | https://www.mdpi.com/1420-3049/29/21/5165 |
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