Thomas C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD, USA.
Department of Biochemistry and Molecular Biology and the Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA.
Nat Struct Mol Biol. 2022 Feb;29(2):121-129. doi: 10.1038/s41594-021-00719-x. Epub 2022 Feb 16.
Chromatin remodelers are ATP-dependent enzymes that reorganize nucleosomes within all eukaryotic genomes. Here we report a complex of the Chd1 remodeler bound to a nucleosome in a nucleotide-free state, determined by cryo-EM to 2.3 Å resolution. The remodeler stimulates the nucleosome to absorb an additional nucleotide on each strand at two different locations: on the tracking strand within the ATPase binding site and on the guide strand one helical turn from the ATPase motor. Remarkably, the additional nucleotide on the tracking strand is associated with a local transformation toward an A-form geometry, explaining how sequential ratcheting of each DNA strand occurs. The structure also reveals a histone-binding motif, ChEx, which can block opposing remodelers on the nucleosome and may allow Chd1 to participate in histone reorganization during transcription.
染色质重塑因子是一类依赖于 ATP 的酶，它们可以重排所有真核生物基因组中的核小体。在这里，我们报告了一个 Chd1 重塑因子复合物与无核苷酸状态下的核小体结合的复合物，通过 cryo-EM 解析到 2.3 Å 的分辨率。该重塑因子刺激核小体在两个不同位置吸收每个链上的额外核苷酸：在 ATP 结合位点内的跟踪链上，以及在距 ATP 酶马达一个螺旋的引导链上。值得注意的是，跟踪链上的额外核苷酸与局部向 A 型构象的转变相关，解释了每个 DNA 链如何顺序棘轮式运动。该结构还揭示了一个组蛋白结合基序 ChEx，它可以阻止核小体上的相反的重塑因子，并可能允许 Chd1 在转录过程中参与组蛋白重组。
