Histones:: A novel class of lipopolysaccharide-binding molecules
Histones:: A novel class of lipopolysaccharide-binding molecules
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DOI：
10.1021/bi0268394
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发表时间：
2003-04-08
期刊：
影响因子：
2.9
通讯作者：
Chaby, R
中科院分区：
文献类型：
--
作者：
Augusto, LA;Decottignies, P;Chaby, R
与可溶性和膜形式的脂多糖（LPS）结合蛋白不同，细胞内脂多糖结合分子文献很少。我们在小鼠肺上皮细胞系中寻找这样的分子。分离到具有lps结合活性的两个蛋白，质谱分析明确鉴定为组蛋白H2A.1和H4。合成的代表部分结构的肽表明LPS结合位点位于组蛋白的c端。进一步研究，我们发现犊牛胸腺组蛋白HI、H2A、H2B、H3、H4均能结合LPS。通过等温滴定量热法测定，LPS与巨噬细胞的结合具有特异性，亲和力（除H4外）高于与LPS结合的抗生素多粘菌素b。在H2A的存在下，LPS与巨噬细胞RAW 264.7的结合以及LPS诱导的细胞产生tnf - α和一氧化氮的能力显著降低。因此，历史可能代表了一类新的细胞内和细胞外LPS传感器。
Unlike soluble and membrane forms of lipopolysaccharide (LPS)-binding proteins, intracellular LPS-binding molecules are poorly documented. We looked for such molecules in a murine lung epithelial cell line. Two proteins with LPS-binding activity were isolated and unambiguously identified as histones H2A.1 and H4 by mass spectrometry. Synthetic peptides representing partial structures indicated that the LPS binding site is located in the C-terminal moiety of the histones. Extending the study, we found that histones HI, H2A, H2B, H3, and H4 from calf thymus are all able to bind LPS. Bindings were specific, and affinities, determined by isothermal titration calorimetry, were (except for H4) higher than that of the LPS-binding antibiotic polymyxin B. In the presence of H2A the binding of LPS to the macrophage cell line RAW 264.7, and the LPS-induced production of TNF-alpha and nitric oxide by these cells, were markedly reduced. Histories may thus represent a new class of intracellular and extracellular LPS sensors.