Nucleoid-associated proteins (NAPs) are crucial in organizing prokaryotic DNA and regulating genes. Vital to these activities are complex nucleoprotein structures, however, how these form remains unclear. Integration host factor (IHF) is an Escherichia coli NAP that creates very sharp bends in DNA at sequences relevant to several functions including transcription and recombination, and is also responsible for general DNA compaction when bound non-specifically. We show that IHF–DNA structural multimodality is more elaborate than previously thought, and provide insights into how this drives mechanical switching towards strongly bent DNA. Using single-molecule atomic force microscopy and atomic molecular dynamics simulations we find three binding modes in roughly equal proportions: ‘associated’ (73° of DNA bend), ‘half-wrapped’ (107°) and ‘fully-wrapped’ (147°), only the latter occurring with sequence specificity. We show IHF bridges two DNA double helices through non-specific recognition that gives IHF a stoichiometry greater than one and enables DNA mesh assembly. We observe that IHF-DNA structural multiplicity is driven through non-specific electrostatic interactions that we anticipate to be a general NAP feature for physical organization of chromosomes.

中文翻译：

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整合宿主因子以多种结合模式弯曲和桥接 DNA，具有不同的特异性

类核相关蛋白 (NAP) 在组织原核 DNA 和调节基因方面至关重要。对这些活动至关重要的是复杂的核蛋白结构，然而，这些形式是如何形成的仍不清楚。整合宿主因子 (IHF) 是一种大肠杆菌 NAP，它在 DNA 中与包括转录和重组在内的多种功能相关的序列中产生非常尖锐的弯曲，并且在非特异性结合时也负责一般的 DNA 压缩。我们展示了 IHF-DNA 结构多模态比以前认为的更精细，并提供了有关这如何推动机械转换为强弯曲 DNA 的见解。使用单分子原子力显微镜和原子分子动力学模拟，我们发现了三种大致相等比例的结合模式：“相关”（DNA 弯曲 73°），“半包裹”（107°）和“完全包裹”（147°），只有后者具有序列特异性。我们展示了 IHF 通过非特异性识别桥接两个 DNA 双螺旋，这使 IHF 的化学计量大于一并能够组装 DNA 网格。我们观察到 IHF-DNA 结构多样性是通过非特异性静电相互作用驱动的，我们预计这将是染色体物理组织的一般 NAP 特征。