Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, Lavrentiev Ave. 8, 630090 Novosibirsk, Russia.
G. B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Brunch of the Russian Academy of Sciences, 159 Pr. 100 let Vladivostoku, 690022 Vladivostok, Russia.
Molecules. 2021 Jan 9;26(2):316. doi: 10.3390/molecules26020316.
Histones play important roles in chromatin functioning and gene transcription, but in the intercellular space, they are harmful since they stimulate systemic inflammatory and toxic responses. Electrophoretically homogeneous IgGs against myelin basic protein (MBP), as well as H3 and H4 histones, were isolated from sera of HIV-infected patients. In contrast to known classical proteases, these IgGs split exclusively only histones and MBP but no other control proteins. Among 13 sites of hydrolysis of H3 by IgGs against H3 and 14 sites for anti-MBP IgGs, only two sites of the hydrolysis were the same. Between seven cleavage sites of H4 with IgGs against H4 and 9 sites of this histone hydrolysis by antibodies against MBP, only three sites were the same. The sites of hydrolysis of H3 (and H4) with abzymes against these histones and against MBP were different, but several expended protein clusters containing hydrolysis sites are partially overlapped. The existence of enzymatic cross-reactivity of abzymes against H3 and H4 and MBP represents a great menace to humans since due to cell apoptosis, histones constantly occur in human blood. They can hydrolyze MBP of the myelin sheath of axons and play a negative role in the pathogenesis of HIV-infected patients.
组蛋白在染色质功能和基因转录中发挥重要作用，但在细胞外空间，它们是有害的，因为它们会刺激全身炎症和毒性反应。从 HIV 感染患者的血清中分离出针对髓鞘碱性蛋白 (MBP)、H3 和 H4 组蛋白的电泳均一 IgG。与已知的经典蛋白酶不同，这些 IgG 仅特异性地切割组蛋白和 MBP，但不切割其他对照蛋白。在针对 H3 的 IgG 水解 H3 的 13 个位点和针对 MBP 的 IgG 水解 MBP 的 14 个位点中，只有两个水解位点相同。针对 H4 的 IgG 水解 H4 的 7 个位点和针对 MBP 的抗体水解该组蛋白的 9 个位点中，只有 3 个位点相同。针对这些组蛋白和 MBP 的 abzyme 水解 H3（和 H4）的位点不同，但含有水解位点的几个扩展蛋白簇部分重叠。针对 H3 和 H4 以及 MBP 的 abzyme 的酶交叉反应的存在对人类构成了巨大威胁，因为由于细胞凋亡，组蛋白会不断出现在人血液中。它们可以水解轴突髓鞘的 MBP，并在 HIV 感染患者的发病机制中发挥负面作用。
