Multiple Sclerosis: Enzymatic Cross Site-Specific Hydrolysis of H1 Histone by IgGs against H1, H2A, H2B, H3, H4 Histones, and Myelin Basic Protein
Histones play a key role in chromatin remodeling and gene transcription. Further, free histones in the blood act as damage-associated molecules. Administration of histones to animals results in systemic inflammatory and toxic effects. Myelin basic protein is the principal constituent element of the...
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MDPI AG
2021-08-01
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| Series: | Biomolecules |
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| author | Georgy A. Nevinsky Svetlana V. Baranova Valentina N. Buneva Pavel S. Dmitrenok |
| author_facet | Georgy A. Nevinsky Svetlana V. Baranova Valentina N. Buneva Pavel S. Dmitrenok |
| author_sort | Georgy A. Nevinsky |
| collection | DOAJ |
| description | Histones play a key role in chromatin remodeling and gene transcription. Further, free histones in the blood act as damage-associated molecules. Administration of histones to animals results in systemic inflammatory and toxic effects. Myelin basic protein is the principal constituent element of the myelin-proteolipid sheath of axons. Abzymes (antibodies with catalytic activities) are the original features of some autoimmune diseases. In this study, electrophoretically homogeneous IgGs against H1, H2A, H2B, H3, and H4 histones and myelin basic protein (MBP) were isolated from the blood sera of multiple sclerosis (MS) patients by several affinity chromatographies. Using MALDI mass spectrometry, the sites of H1 histone cleavage by IgGs against H1, H2A, H2B, H3, H4, and MBP were determined. It was shown that IgGs against H1 split H1 at 12 sites, while the number of cleavage sites by abzymes against other histones was lower: H2A (9), H2B (7), H3 (3), and H4 (3). The minimum rate of H1 hydrolysis was observed for antibodies against H3 and H4. A high rate of hydrolysis and the maximum number of H1 hydrolysis sites (17) were found for antibodies against MBP. Only a few sites of H1 hydrolysis by anti-H1 antibodies coincided with those for IgGs against H2A, H2B, H3, H4, and MBP. Thus, the polyreactivity of complexation and the enzymatic cross-activity of antibodies against H1, four other histones, and MBP have first been shown. Since histones act as damage molecules, abzymes against histones and MBP can play a negative role in the pathogenesis of MS and probably other different diseases as well. |
| first_indexed | 2024-03-10T08:58:43Z |
| format | Article |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T08:58:43Z |
| publishDate | 2021-08-01 |
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| series | Biomolecules |
| spelling | doaj.art-b2b079439cf34d0b942f7bca6546abb92023-11-22T06:55:24ZengMDPI AGBiomolecules2218-273X2021-08-01118114010.3390/biom11081140Multiple Sclerosis: Enzymatic Cross Site-Specific Hydrolysis of H1 Histone by IgGs against H1, H2A, H2B, H3, H4 Histones, and Myelin Basic ProteinGeorgy A. Nevinsky0Svetlana V. Baranova1Valentina N. Buneva2Pavel S. Dmitrenok3Siberian Division, Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Lavrentiev Ave. 8, 630090 Novosibirsk, RussiaSiberian Division, Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Lavrentiev Ave. 8, 630090 Novosibirsk, RussiaSiberian Division, Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Lavrentiev Ave. 8, 630090 Novosibirsk, RussiaFar East Division, Pacific Institute of Bioorganic Chemistry, Russian Academy of Sciences, 690022 Vladivostok, RussiaHistones play a key role in chromatin remodeling and gene transcription. Further, free histones in the blood act as damage-associated molecules. Administration of histones to animals results in systemic inflammatory and toxic effects. Myelin basic protein is the principal constituent element of the myelin-proteolipid sheath of axons. Abzymes (antibodies with catalytic activities) are the original features of some autoimmune diseases. In this study, electrophoretically homogeneous IgGs against H1, H2A, H2B, H3, and H4 histones and myelin basic protein (MBP) were isolated from the blood sera of multiple sclerosis (MS) patients by several affinity chromatographies. Using MALDI mass spectrometry, the sites of H1 histone cleavage by IgGs against H1, H2A, H2B, H3, H4, and MBP were determined. It was shown that IgGs against H1 split H1 at 12 sites, while the number of cleavage sites by abzymes against other histones was lower: H2A (9), H2B (7), H3 (3), and H4 (3). The minimum rate of H1 hydrolysis was observed for antibodies against H3 and H4. A high rate of hydrolysis and the maximum number of H1 hydrolysis sites (17) were found for antibodies against MBP. Only a few sites of H1 hydrolysis by anti-H1 antibodies coincided with those for IgGs against H2A, H2B, H3, H4, and MBP. Thus, the polyreactivity of complexation and the enzymatic cross-activity of antibodies against H1, four other histones, and MBP have first been shown. Since histones act as damage molecules, abzymes against histones and MBP can play a negative role in the pathogenesis of MS and probably other different diseases as well.https://www.mdpi.com/2218-273X/11/8/1140human blood sera antibodiesmultiple sclerosis patientscatalytic antibodies-abzymeshydrolysis of H1 histoneIgGs against H1H2A |
| spellingShingle | Georgy A. Nevinsky Svetlana V. Baranova Valentina N. Buneva Pavel S. Dmitrenok Multiple Sclerosis: Enzymatic Cross Site-Specific Hydrolysis of H1 Histone by IgGs against H1, H2A, H2B, H3, H4 Histones, and Myelin Basic Protein Biomolecules human blood sera antibodies multiple sclerosis patients catalytic antibodies-abzymes hydrolysis of H1 histone IgGs against H1 H2A |
| title | Multiple Sclerosis: Enzymatic Cross Site-Specific Hydrolysis of H1 Histone by IgGs against H1, H2A, H2B, H3, H4 Histones, and Myelin Basic Protein |
| title_full | Multiple Sclerosis: Enzymatic Cross Site-Specific Hydrolysis of H1 Histone by IgGs against H1, H2A, H2B, H3, H4 Histones, and Myelin Basic Protein |
| title_fullStr | Multiple Sclerosis: Enzymatic Cross Site-Specific Hydrolysis of H1 Histone by IgGs against H1, H2A, H2B, H3, H4 Histones, and Myelin Basic Protein |
| title_full_unstemmed | Multiple Sclerosis: Enzymatic Cross Site-Specific Hydrolysis of H1 Histone by IgGs against H1, H2A, H2B, H3, H4 Histones, and Myelin Basic Protein |
| title_short | Multiple Sclerosis: Enzymatic Cross Site-Specific Hydrolysis of H1 Histone by IgGs against H1, H2A, H2B, H3, H4 Histones, and Myelin Basic Protein |
| title_sort | multiple sclerosis enzymatic cross site specific hydrolysis of h1 histone by iggs against h1 h2a h2b h3 h4 histones and myelin basic protein |
| topic | human blood sera antibodies multiple sclerosis patients catalytic antibodies-abzymes hydrolysis of H1 histone IgGs against H1 H2A |
| url | https://www.mdpi.com/2218-273X/11/8/1140 |
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