title: Antibodies to H1 histone from the sera of HIV-infected patients recognize and catalyze site-specific degradation of this histone.
abstract: Histones and their posttranslational modifications have key roles in chromatin remodeling and gene transcription. Besides intranuclear functions, histones act as damage-associated molecules when they are released into the extracellular space. Administration of histones to animals leads to systemic inflammatory and toxic responses. Autoantibodies with enzymatic activities (abzymes) are distinctive feature of some autoimmune and viral diseases. Electrophoretically and immunologically homogeneous IgGs containing no canonical enzymes were isolated from sera of human immunodeficiency virus-infected patients by chromatography on several affinity sorbents. In contrast to canonical proteases (trypsin, chymotrypsin, and proteinase K), IgGs from human immunodeficiency virus-infected patients purified by affinity chromatography on Sepharose containing immobilized histones specifically recognized and hydrolyzed only histones but not many other tested globular proteins. Using matrix-assisted laser desorption/ionization mass spectrometry, the sites of H1 histone (193 amino acids [AAs]) cleavage by anti-H1 histone IgGs were determined for the first time. It was shown that 1 cluster of 2 major and 4 moderate sites of cleavage is located at the beginning (106-112 AAs) of the known antigenic determinants disposed at the long C-terminal sequence of H1. Two clusters of minor and very weak sites of the protein cleavage correspond to middle (8 sites, 138-158 AAs) and terminal (5 sites, 166-176 AAs) parts of the antigenic determinants. It was shown that in contrast to canonical proteases, N-terminal part of H1 histone (1-136 AAs) containing no antigenic determinants is an unpredictably very resistant against hydrolysis by abzymes, while it can be easily cleavage by canonical proteases. Because histones act as damage-associated molecules, abzymes against H1 and other histones can play important role in pathogenesis of acquired immune deficiency syndrome and probably other different diseases.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, Lavrentiev Ave. 8, 630090, Novosibirsk, Russia.
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Baranova
authors.affiliation: Pacific Institute of Bioorganic Chemistry, Far East Division, Russian Academy of Sciences, Vladivostok, 690022, Russia.
authors.forename: Pavel S
authors.initials: PS
authors.lastname: Dmitrienok
authors.affiliation: Institute of Cytology and Genetics, Siberian Division of Russian Academy of Sciences, 10 Lavrentiev Ave., 630090, Novosibirsk, Russia.
authors.forename: Nikita V
authors.initials: NV
authors.lastname: Ivanisenko
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, Lavrentiev Ave. 8, 630090, Novosibirsk, Russia.
authors.forename: Valentina N
authors.initials: VN
authors.lastname: Buneva
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, Lavrentiev Ave. 8, 630090, Novosibirsk, Russia.
authors.forename: Georgy A
authors.initials: GA
authors.lastname: Nevinsky
mesh_terms: D000328:Adult; D020816:Amino Acid Motifs; D001665:Binding Sites; D002384:Catalysis; D002846:Chromatography, Affinity; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism*; D008297:Male; D008958:Models, Molecular; D059748:Proteolysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity; D055815:Young Adult
chemical_list: D006657:Histones; D007074:Immunoglobulin G
keywords: HIV-infected patients; catalytic antibodies; human blood antibodies; hydrolysis of H1 histone