Section of Structural Biology, Department of Medicine, Imperial College London, London SW7 2AZ, UK.
Single Molecule Imaging Group, MRC London Institute of Medical Sciences, London W12 0NN, UK.
Science. 2018 Oct 12;362(6411). doi: 10.1126/science.aat7716.
The yeast SWR1 complex exchanges histone H2A in nucleosomes with Htz1 (H2A.Z in humans). The cryo-electron microscopy structure of the SWR1 complex bound to a nucleosome at 3.6-angstrom resolution reveals details of the intricate interactions between components of the SWR1 complex and its nucleosome substrate. Interactions between the Swr1 motor domains and the DNA wrap at superhelical location 2 distort the DNA, causing a bulge with concomitant translocation of the DNA by one base pair, coupled to conformational changes of the histone core. Furthermore, partial unwrapping of the DNA from the histone core takes place upon binding of nucleosomes to SWR1 complex. The unwrapping, as monitored by single-molecule data, is stabilized and has its dynamics altered by adenosine triphosphate binding but does not require hydrolysis.
酵母 SWR1 复合物将核小体中的组蛋白 H2A 与 Htz1（人类中的 H2A.Z）交换。通过 3.6 埃分辨率的冷冻电子显微镜结构观察到 SWR1 复合物与核小体结合的结构，揭示了 SWR1 复合物及其核小体底物之间复杂相互作用的细节。Swr1 马达结构域与超螺旋位置 2 的 DNA 缠绕之间的相互作用使 DNA发生扭曲，导致 DNA 产生一个碱基对的凸起，同时伴随着 DNA 的移位，这与组蛋白核心的构象变化相关。此外，当核小体与 SWR1 复合物结合时，部分 DNA 从组蛋白核心上解缠绕。通过单分子数据监测到的解缠绕过程，在结合 ATP 时会被稳定下来，并且其动力学会发生改变，但不需要水解。
