The condensin protein complex compacts chromatin during mitosis using its DNA-loop extrusion activity. Previous studies proposed scrunching and loop-capture models as molecular mechanisms for the loop extrusion process, both of which assume the binding of double-strand (ds) DNA to the so-called hinge domain formed at the interface of the condensin subunits Smc2 and Smc4. However, how the hinge domain contacts dsDNA has remained unknown, potentially due to its conformational plasticity. Here, we conducted atomic force microscopy imaging of the budding yeast condensin holo-complex and used this data as basis for coarse-grained molecular dynamics simulations to model the hinge structure in a transient open conformation. We then simulated the dsDNA binding to open and closed hinge conformations, predicting that dsDNA binds to the outside surface when closed and to the outside and inside surfaces when open. Our simulations also suggested that the hinge can close around dsDNA bound to the inside surface. The conformational change of the hinge domain might be essential for the dsDNA binding regulation and play important roles in condensin-mediated DNA-loop extrusion.

中文翻译：

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使用原子力显微镜指导的分子动力学模拟，建立与凝缩蛋白铰链结构域结合的DNA建模

condensin蛋白复合物利用其DNA环挤出活性可在有丝分裂过程中压缩染色质。先前的研究提出了收缩和环捕获模型作为环挤出过程的分子机制，两者均假设双链（ds）DNA与在凝集素亚基Smc2和Smc4界面形成的所谓铰链域结合。然而，铰链结构域如何与dsDNA接触仍然是未知的，这可能是由于其构象可塑性。在这里，我们对发芽的酵母凝缩素整体复合物进行了原子力显微镜成像，并使用此数据作为粗粒分子动力学模拟的基础，以模拟瞬时开放构象中的铰链结构。然后，我们模拟了dsDNA与打开和关闭铰链构象的结合，预测dsDNA在关闭时会绑定到外表面，在打开时会绑定到外表面和内表面。我们的模拟还表明，铰链可以在与内表面结合的dsDNA周围闭合。铰链结构域的构象变化可能对dsDNA结合调控至关重要，并在凝集素介导的DNA环挤出中发挥重要作用。