NuA4 is the only essential acetyltransferase in yeast that can catalyze the acetylation of the histones H2A, H2A.Z, and H4, thereby affecting gene transcription. However, the acetylation process of NuA4, such as how NuA4 acetylates H4 and H2A.Z differently, remains largely elusive. Here, using cryoelectron microscopy (cryo-EM) single particle analysis, we present seven cryo-EM structures of piccolo NuA4 (pNuA4) in complex with wild-type H2A.Z or H2A.Z-mutant-containing nucleosomes in the absence or presence of acetyl coenzyme A (Ac-CoA). We revealed that, in the absence of Ac-CoA, pNuA4 adopts multiple conformations to search for its substrates. After adding Ac-CoA, the single-molecule Förster resonance energy transfer (smFRET) and cryo-EM data indicated that pNuA4 prefers to bind H4 and undergoes a dynamic conformational change to complete the acetylation. We also obtained previously unseen structures in states associated with the acetylation of H2A.Z. These cryo-EM structures and smFRET results suggest a complex acetylation process on H4 and H2A.Z by pNuA4. The results provide a comprehensive picture of the mechanism by which pNuA4 acetylates its substrates within an H2A.Z-containing nucleosome.

中文翻译：

---

冷冻电镜结构揭示了短笛 NuA4 的乙酰化过程


NuA4 是酵母中唯一可以催化组蛋白 H2A、H2A 乙酰化的必需乙酰转移酶。Z 和 H4，从而影响基因转录。然而，NuA4 的乙酰化过程，例如 NuA4 如何乙酰化 H4 和 H2A。Z 的 Z 值在很大程度上仍然难以捉摸。在这里，使用冷冻电子显微镜 （cryo-EM） 单颗粒分析，我们展示了短笛 NuA4 （pNuA4） 与野生型 H 2 A 复合物的七种冷冻电镜结构。Z 或 H2A。在不存在或存在乙酰辅酶 A （Ac-CoA） 的情况下含有 Z 突变体的核小体。我们发现，在没有 Ac-CoA 的情况下，pNuA4 采用多种构象来寻找其底物。添加 Ac-CoA 后，单分子 Förster 共振能量转移 （smFRET） 和冷冻电镜数据表明，pNuA4 更喜欢结合 H4 并经历动态构象变化以完成乙酰化。我们还获得了与 H2A.Z 乙酰化相关的状态中以前未见过的结构。这些冷冻电镜结构和 smFRET 结果表明 H4 和 H2A 上存在复杂的乙酰化过程。p NuA4 的 Z。结果全面介绍了 pNuA4 在 H2A 中乙酰化其底物的机制。含 Z 的核小体。