Department of Integrated Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404, Illkirch, France.
Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France.
Nat Commun. 2017 Nov 16;8(1):1556. doi: 10.1038/s41467-017-01564-7.
The transcription co-activator complex SAGA is recruited to gene promoters by sequence-specific transcriptional activators and by chromatin modifications to promote pre-initiation complex formation. The yeast Tra1 subunit is the major target of acidic activators such as Gal4, VP16, or Gcn4 but little is known about its structural organization. The 430 kDa Tra1 subunit and its human homolog the transformation/transcription domain-associated protein TRRAP are members of the phosphatidyl 3-kinase-related kinase (PIKK) family. Here, we present the cryo-EM structure of the entire SAGA complex where the major target of activator binding, the 430 kDa Tra1 protein, is resolved with an average resolution of 5.7 Å. The high content of alpha-helices in Tra1 enabled tracing of the majority of its main chain. Our results highlight the integration of Tra1 within the major epigenetic regulator SAGA.
转录共激活因子复合物 SAGA 通过序列特异性转录激活因子和染色质修饰被招募到基因启动子，以促进起始前复合物的形成。酵母 Tra1 亚基是酸性激活剂（如 Gal4、VP16 或 Gcn4）的主要靶标，但对其结构组织知之甚少。430kDa Tra1 亚基及其人类同源物转化/转录结构域相关蛋白 TRRAP 是磷脂酰 3-激酶相关激酶（PIKK）家族的成员。在这里，我们展示了整个 SAGA 复合物的冷冻电镜结构，其中激活剂结合的主要靶标，430kDa Tra1 蛋白，以平均分辨率 5.7Å解析。Tra1 中大量的α-螺旋使其大部分主链得以追踪。我们的结果强调了 Tra1 在主要表观遗传调节剂 SAGA 中的整合。
