帮我介绍下以下这个蛋白的结构、功能、疾病、背景研究方面信息： 中文名称:高迁移率族蛋白B1 英文全称:High Mobility Group Protein B1 简称:HMGB-1

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HMGB1, or High Mobility Group Protein B1, is a highly conserved nuclear protein found in all eukaryotic cells. With a molecular weight of 25 kilodaltons and consisting of 215 amino acids, HMGB1 serves dual roles as both a nuclear chromatin-binding protein and an extracellular danger signal. This versatile protein plays crucial roles in gene regulation, DNA repair, and immune responses, making it a key player in cellular biology and disease pathology. HMGB1 consists of three distinct functional domains. The protein contains two highly similar DNA-binding domains called HMG Box A and HMG Box B, spanning amino acids 1 to 79 and 89 to 162 respectively. Each HMG box adopts an L-shaped structure that allows specific binding to the minor groove of DNA. The third domain is an acidic C-terminal tail from amino acids 163 to 215, which plays a crucial regulatory role in modulating protein-DNA interactions and protein-protein interactions. In the nucleus, HMGB1 functions as a crucial chromatin architectural protein. It binds to the minor groove of DNA and induces dramatic structural changes, bending DNA by approximately 90 degrees. This bending activity facilitates nucleosome dynamics, enhances transcriptional processes, and promotes chromatin remodeling. HMGB1 also plays essential roles in DNA repair by helping to recruit repair machinery and stabilizing protein-DNA complexes during the repair process. HMGB1 exhibits a dual nature, functioning not only as a nuclear protein but also as an extracellular danger signal known as a DAMP or damage-associated molecular pattern. When cells undergo stress, damage, or death, HMGB1 is released into the extracellular space through passive release during necrosis or active secretion by immune cells. Once outside the cell, HMGB1 binds to pattern recognition receptors including TLR2, TLR4, and RAGE on immune cells, triggering inflammatory cascades that lead to cytokine production and immune cell recruitment to sites of tissue damage. 高迁移率族蛋白B1，简称HMGB1，是一种重要的多功能蛋白质。它在正常情况下位于细胞核内，参与DNA的结构调节和转录调节。当细胞受损或死亡时，HMGB1会释放到细胞外，作为损伤相关分子模式发挥炎症介质的作用。 HMGB1是一个相对较小的蛋白质，分子量约30千道尔顿，由215个氨基酸组成。它具有独特的结构域组成：N端的A-box域主要负责DNA结合和弯曲，中间的B-box域具有细胞因子活性，而C末端的酸性尾部则调节蛋白质的活性。这种结构使HMGB1能够同时发挥核内和核外的多种功能。 HMGB1具有独特的双重功能特性。在细胞核内，它作为结构蛋白参与DNA的结合和弯曲，调节基因转录，并参与染色质重塑和DNA修复过程。当细胞受损或死亡时，HMGB1会被释放到细胞外，此时它转变为一种强有力的促炎细胞因子，激活免疫系统，促进炎症反应和组织修复。 HMGB1的研究历程经历了几个重要阶段。1973年首次发现这种蛋白质，1999年确定其促炎细胞因子功能，2003年发现它与RAGE受体的结合机制，2010年代确立其作为治疗靶点的潜力。目前，HMGB1在多种疾病中的作用机制成为研究热点，包括败血症、癌症、自身免疫疾病和神经退行性疾病等。 HMGB1在各种疾病病理学中发挥关键作用。在败血症和全身性炎症中，升高的HMGB1水平既是疾病严重程度的生物标记物，也是疾病进展的介质。在癌症中，HMGB1促进肿瘤进展、转移和血管生成。类风湿关节炎和系统性红斑狼疮等自身免疫疾病显示HMGB1活性增加，导致慢性炎症。在神经退行性疾病包括阿尔茨海默病和中风中，HMGB1介导神经炎症和组织损伤，使其成为多种疾病治疗的关键靶点。