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Multiple Sclerosis: Enzymatic Cross Site-Specific Recognition and Hydrolysis of H3 Histone by IgGs against H3, H1, H2A, H2B, H4 Histones, Myelin Basic Protein, and DNA

Histones have a specific key role in the remodeling of chromatin and gene transcription. In the blood, free histones are damage-connected proteins. Myelin basic protein (MBP) is the major component of the myelin-proteolipid sheath of axons. Antibodies possessing enzymatic activities (abzymes, ABZs)...

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Autores principales: Nevinsky, Georgy A., Buneva, Valentina N., Dmitrenok, Pavel S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599260/
https://www.ncbi.nlm.nih.gov/pubmed/36289924
http://dx.doi.org/10.3390/biomedicines10102663
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author Nevinsky, Georgy A.
Buneva, Valentina N.
Dmitrenok, Pavel S.
author_facet Nevinsky, Georgy A.
Buneva, Valentina N.
Dmitrenok, Pavel S.
author_sort Nevinsky, Georgy A.
collection PubMed
description Histones have a specific key role in the remodeling of chromatin and gene transcription. In the blood, free histones are damage-connected proteins. Myelin basic protein (MBP) is the major component of the myelin-proteolipid sheath of axons. Antibodies possessing enzymatic activities (abzymes, ABZs) are the specific features of several autoimmune pathologies. IgGs against five histones, MBP, and DNA were obtained from the sera of multiple sclerosis (MS) patients using several affinity chromatographies. The sites of H3 histone splitting by Abs against five individual histones, MBP, and DNA were revealed by MALDI mass spectrometry. It was shown that the number of H3 splitting sites by IgGs against five various histones is different (number of sites): H3 (11), H1 (14), H2A (11), H4 (17), MBP (22), and DNA (29). IgGs against five different histones hydrolyze H3 at different sites, and only a few them coincide. The main reason for the enzymatic cross-reactivity of Abs against H3 and four other histones, as well as MBP, might be the high level of these proteins’ homology. The effective hydrolysis of the H3 histone at 29 sites with IgGs against DNA can be explained by the formation of chimeric abzymes against hybrid antigenic determinants formed by different histones and MBP at the junction of these protein sequences with DNA. The active centers of such abzymes contain structural elements of canonical DNases and proteases. Since free histones are pernicious proteins, antibodies–ABZs against five histones, MBP, and DNA could have a negative role in the pathogenesis of MS and probably other various autoimmune diseases.
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spelling pubmed-95992602022-10-27 Multiple Sclerosis: Enzymatic Cross Site-Specific Recognition and Hydrolysis of H3 Histone by IgGs against H3, H1, H2A, H2B, H4 Histones, Myelin Basic Protein, and DNA Nevinsky, Georgy A. Buneva, Valentina N. Dmitrenok, Pavel S. Biomedicines Article Histones have a specific key role in the remodeling of chromatin and gene transcription. In the blood, free histones are damage-connected proteins. Myelin basic protein (MBP) is the major component of the myelin-proteolipid sheath of axons. Antibodies possessing enzymatic activities (abzymes, ABZs) are the specific features of several autoimmune pathologies. IgGs against five histones, MBP, and DNA were obtained from the sera of multiple sclerosis (MS) patients using several affinity chromatographies. The sites of H3 histone splitting by Abs against five individual histones, MBP, and DNA were revealed by MALDI mass spectrometry. It was shown that the number of H3 splitting sites by IgGs against five various histones is different (number of sites): H3 (11), H1 (14), H2A (11), H4 (17), MBP (22), and DNA (29). IgGs against five different histones hydrolyze H3 at different sites, and only a few them coincide. The main reason for the enzymatic cross-reactivity of Abs against H3 and four other histones, as well as MBP, might be the high level of these proteins’ homology. The effective hydrolysis of the H3 histone at 29 sites with IgGs against DNA can be explained by the formation of chimeric abzymes against hybrid antigenic determinants formed by different histones and MBP at the junction of these protein sequences with DNA. The active centers of such abzymes contain structural elements of canonical DNases and proteases. Since free histones are pernicious proteins, antibodies–ABZs against five histones, MBP, and DNA could have a negative role in the pathogenesis of MS and probably other various autoimmune diseases. MDPI 2022-10-21 /pmc/articles/PMC9599260/ /pubmed/36289924 http://dx.doi.org/10.3390/biomedicines10102663 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nevinsky, Georgy A.
Buneva, Valentina N.
Dmitrenok, Pavel S.
Multiple Sclerosis: Enzymatic Cross Site-Specific Recognition and Hydrolysis of H3 Histone by IgGs against H3, H1, H2A, H2B, H4 Histones, Myelin Basic Protein, and DNA
title Multiple Sclerosis: Enzymatic Cross Site-Specific Recognition and Hydrolysis of H3 Histone by IgGs against H3, H1, H2A, H2B, H4 Histones, Myelin Basic Protein, and DNA
title_full Multiple Sclerosis: Enzymatic Cross Site-Specific Recognition and Hydrolysis of H3 Histone by IgGs against H3, H1, H2A, H2B, H4 Histones, Myelin Basic Protein, and DNA
title_fullStr Multiple Sclerosis: Enzymatic Cross Site-Specific Recognition and Hydrolysis of H3 Histone by IgGs against H3, H1, H2A, H2B, H4 Histones, Myelin Basic Protein, and DNA
title_full_unstemmed Multiple Sclerosis: Enzymatic Cross Site-Specific Recognition and Hydrolysis of H3 Histone by IgGs against H3, H1, H2A, H2B, H4 Histones, Myelin Basic Protein, and DNA
title_short Multiple Sclerosis: Enzymatic Cross Site-Specific Recognition and Hydrolysis of H3 Histone by IgGs against H3, H1, H2A, H2B, H4 Histones, Myelin Basic Protein, and DNA
title_sort multiple sclerosis: enzymatic cross site-specific recognition and hydrolysis of h3 histone by iggs against h3, h1, h2a, h2b, h4 histones, myelin basic protein, and dna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599260/
https://www.ncbi.nlm.nih.gov/pubmed/36289924
http://dx.doi.org/10.3390/biomedicines10102663
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