Joyeux Marc
Laboratoire Interdisciplinaire de Physique, CNRS and Université Grenoble Alpes, St Martin d'Hères, France.
Front Microbiol. 2023 Feb 28;14:1116776. doi: 10.3389/fmicb.2023.1116776. eCollection 2023.
The genomic DNA of bacteria occupies only a fraction of the cell called the nucleoid, although it is not bounded by any membrane and would occupy a volume hundreds of times larger than the cell in the absence of constraints. The two most important contributions to the compaction of the DNA coil are the cross-linking of the DNA by nucleoid proteins (like H-NS and StpA) and the demixing of DNA and other abundant globular macromolecules which do not bind to the DNA (like ribosomes). The present work deals with the interplay of DNA-bridging proteins and globular macromolecular crowders, with the goal of determining the extent to which they collaborate in organizing the nucleoid. In order to answer this question, a coarse-grained model was developed and its properties were investigated through Brownian dynamics simulations. These simulations reveal that the radius of gyration of the DNA coil decreases linearly with the effective volume ratio of globular crowders and the number of DNA bridges formed by nucleoid proteins in the whole range of physiological values. Moreover, simulations highlight the fact that the number of DNA bridges formed by nucleoid proteins depends crucially on their ability to self-associate (oligomerize). An explanation for this result is proposed in terms of the mean distance between DNA segments and the capacity of proteins to maintain DNA-bridging in spite of the thermal fluctuations of the DNA network. Finally, simulations indicate that non-associating proteins preserve a high mobility inside the nucleoid while contributing to its compaction, leading to a DNA/protein complex which looks like a liquid droplet. In contrast, self-associating proteins form a little deformable network which cross-links the DNA chain, with the consequence that the DNA/protein complex looks more like a gel.
细菌的基因组DNA仅占据细胞内称为类核的一部分，尽管它没有被任何膜所包围，并且在没有限制的情况下其占据的体积将比细胞大数百倍。对DNA螺旋压缩的两个最重要贡献是类核蛋白（如H-NS和StpA）对DNA的交联以及DNA与其他不与DNA结合的丰富球状大分子（如核糖体）的相分离。目前的工作涉及DNA桥连蛋白和球状大分子拥挤物之间的相互作用，目的是确定它们在组织类核方面的协作程度。为了回答这个问题，开发了一个粗粒度模型，并通过布朗动力学模拟研究了其性质。这些模拟表明，在整个生理值范围内，DNA螺旋的回转半径随球状拥挤物的有效体积比和类核蛋白形成的DNA桥数量呈线性下降。此外，模拟突出了这样一个事实，即类核蛋白形成的DNA桥数量关键取决于它们的自缔合（寡聚化）能力。根据DNA片段之间的平均距离以及蛋白质在DNA网络热波动情况下维持DNA桥连的能力，对这一结果提出了解释。最后，模拟表明，非缔合蛋白在有助于类核压缩的同时，在类核内部保持高迁移率，形成一种看起来像液滴的DNA/蛋白质复合物。相比之下，自缔合蛋白形成一个几乎不可变形的网络，使DNA链交联，结果是DNA/蛋白质复合物看起来更像凝胶。
