Giardia lamblia is a pathogenic unicellular eukaryotic parasite that causes giardiasis. Its genome encodes the canonical histones H2A, H2B, H3, and H4, which share low amino acid sequence identity with their human orthologues. We determined the structure of the G. lamblia nucleosome core particle (NCP) at 3.6 Å resolution by cryo-electron microscopy. G. lamblia histones form a characteristic NCP, in which the visible 125 base-pair region of the DNA is wrapped in a left-handed supercoil. The acidic patch on the G. lamblia octamer is deeper, due to an insertion extending the H2B α1 helix and L1 loop, and thus cannot bind the LANA acidic patch binding peptide. The DNA and histone regions near the DNA entry-exit sites could not be assigned, suggesting that these regions are asymmetrically flexible in the G. lamblia NCP. Characterization by thermal unfolding in solution revealed that both the H2A–H2B and DNA association with the G. lamblia H3–H4 were weaker than those for human H3–H4. These results demonstrate the uniformity of the histone octamer as the organizing platform for eukaryotic chromatin, but also illustrate the unrecognized capability for large scale sequence variations that enable the adaptability of histone octamer surfaces and confer internal stability.

中文翻译：

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含有贾第鞭毛虫组蛋白的核小体核心颗粒的冷冻电镜结构

贾第鞭毛虫是一种致病性单细胞真核寄生虫，可引起贾第虫病。它的基因组编码典型的组蛋白 H2A、H2B、H3 和 H4，它们与其人类直系同源物具有低氨基酸序列同一性。我们通过低温电子显微镜以 3.6 Å 的分辨率确定了 G. lamblia 核小体核心颗粒 (NCP) 的结构。G. lamblia 组蛋白形成一个特征性的 NCP，其中 DNA 的可见 125 个碱基对区域被包裹在一个左手超螺旋中。由于延伸 H2B α1 螺旋和 L1 环的插入，G. lamblia 八聚体上的酸性斑块更深，因此不能结合 LANA 酸性斑块结合肽。无法分配 DNA 出入口附近的 DNA 和组蛋白区域，这表明这些区域在 G. lamblia NCP 中是不对称灵活的。通过溶液中的热展开表征表明，H2A-H2B 和 DNA 与 G. lamblia H3-H4 的结合都比人类 H3-H4 的弱。这些结果证明了组蛋白八聚体作为真核染色质组织平台的均匀性，但也说明了大规模序列变化的未被识别的能力，这使得组蛋白八聚体表面具有适应性并赋予内部稳定性。