Antibodies towards Tyrosine Amyloid-Like Fibrils Allow Toxicity Modulation and Cellular Imaging of the Assemblies
The amino acid tyrosine forms cytotoxic amyloid-like fibrils by molecular self-assembly. However, the production of antibodies towards tyrosine assemblies, reflecting their presentation to the immune system, was not demonstrated yet. Here, we describe the production of antibodies that specifically r...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-05-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/23/6/1273 |
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| author | Dor Zaguri Topaz Kreiser Shira Shaham-Niv Ehud Gazit |
| author_facet | Dor Zaguri Topaz Kreiser Shira Shaham-Niv Ehud Gazit |
| author_sort | Dor Zaguri |
| collection | DOAJ |
| description | The amino acid tyrosine forms cytotoxic amyloid-like fibrils by molecular self-assembly. However, the production of antibodies towards tyrosine assemblies, reflecting their presentation to the immune system, was not demonstrated yet. Here, we describe the production of antibodies that specifically recognize tyrosine in its fibrillated form. The antibodies were demonstrated to specifically bind self-assembled tyrosine, in contrast to its non-aggregated form or disintegrated fibrils. The antibodies could be used for immunostaining of tyrosine fibrils in cultured cells. Furthermore, confocal microscopy allowed a demonstration of the intracellular presence of the metabolite amyloids in a neuroblastoma cell model. Finally, pre-incubation of tyrosine fibrils with the antibodies resulted in significant reduction in their cytotoxicity. Taken together, we provide an experimental proof for the immunogenicity of tyrosine amyloid fibrillary assemblies. These specific antibodies against tyrosine structures could be further used as a research tool to study the dynamics, toxicity and cellular localization of the assemblies. |
| first_indexed | 2024-12-13T09:29:12Z |
| format | Article |
| id | doaj.art-57b9a3b878394679b62cdd3fad50d799 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-13T09:29:12Z |
| publishDate | 2018-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-57b9a3b878394679b62cdd3fad50d7992022-12-21T23:52:32ZengMDPI AGMolecules1420-30492018-05-01236127310.3390/molecules23061273molecules23061273Antibodies towards Tyrosine Amyloid-Like Fibrils Allow Toxicity Modulation and Cellular Imaging of the AssembliesDor Zaguri0Topaz Kreiser1Shira Shaham-Niv2Ehud Gazit3Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, IsraelDepartment of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, IsraelDepartment of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, IsraelDepartment of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, IsraelThe amino acid tyrosine forms cytotoxic amyloid-like fibrils by molecular self-assembly. However, the production of antibodies towards tyrosine assemblies, reflecting their presentation to the immune system, was not demonstrated yet. Here, we describe the production of antibodies that specifically recognize tyrosine in its fibrillated form. The antibodies were demonstrated to specifically bind self-assembled tyrosine, in contrast to its non-aggregated form or disintegrated fibrils. The antibodies could be used for immunostaining of tyrosine fibrils in cultured cells. Furthermore, confocal microscopy allowed a demonstration of the intracellular presence of the metabolite amyloids in a neuroblastoma cell model. Finally, pre-incubation of tyrosine fibrils with the antibodies resulted in significant reduction in their cytotoxicity. Taken together, we provide an experimental proof for the immunogenicity of tyrosine amyloid fibrillary assemblies. These specific antibodies against tyrosine structures could be further used as a research tool to study the dynamics, toxicity and cellular localization of the assemblies.http://www.mdpi.com/1420-3049/23/6/1273self-assemblytyrosinemetabolite amyloid-like fibrilstyrosinemiainborn error of metabolismimmunogenicityanti-tyr antibodies |
| spellingShingle | Dor Zaguri Topaz Kreiser Shira Shaham-Niv Ehud Gazit Antibodies towards Tyrosine Amyloid-Like Fibrils Allow Toxicity Modulation and Cellular Imaging of the Assemblies Molecules self-assembly tyrosine metabolite amyloid-like fibrils tyrosinemia inborn error of metabolism immunogenicity anti-tyr antibodies |
| title | Antibodies towards Tyrosine Amyloid-Like Fibrils Allow Toxicity Modulation and Cellular Imaging of the Assemblies |
| title_full | Antibodies towards Tyrosine Amyloid-Like Fibrils Allow Toxicity Modulation and Cellular Imaging of the Assemblies |
| title_fullStr | Antibodies towards Tyrosine Amyloid-Like Fibrils Allow Toxicity Modulation and Cellular Imaging of the Assemblies |
| title_full_unstemmed | Antibodies towards Tyrosine Amyloid-Like Fibrils Allow Toxicity Modulation and Cellular Imaging of the Assemblies |
| title_short | Antibodies towards Tyrosine Amyloid-Like Fibrils Allow Toxicity Modulation and Cellular Imaging of the Assemblies |
| title_sort | antibodies towards tyrosine amyloid like fibrils allow toxicity modulation and cellular imaging of the assemblies |
| topic | self-assembly tyrosine metabolite amyloid-like fibrils tyrosinemia inborn error of metabolism immunogenicity anti-tyr antibodies |
| url | http://www.mdpi.com/1420-3049/23/6/1273 |
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