Hefei National Laboratory for Physical Sciences at Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, PR China.
Hefei National Laboratory for Physical Sciences at Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, PR China; Cancer Hospital, Chinese Academy of Science, Hefei, Anhui, PR China.
J Struct Biol. 2020 Jan 1;209(1):107406. doi: 10.1016/j.jsb.2019.107406. Epub 2019 Nov 17.
The essential SAS2-related acetyltransferase 1 (Esa1), as a acetyltransferase of MYST family, is indispensable for the cell cycle and transcriptional regulation. The Tudor domain consists of 60 amino acids and belongs to the Royal family, which serves as a module interacting with methylated histone and/or DNA. Although Tudor domain has been widely studied in higher eukaryotes, its structure and function remain unclear in Trypanosoma brucei (T. brucei), a protozoan unicellular parasite causing sleeping sickness in human and nagana in cattle in sub-Saharan Africa. Here, we determined a high-resolution structure of TbEsa1 presumed Tudor domain from T. brucei by X-ray crystallography. TbEsa1 Tudor domain adopts a conserved Tudor-like fold, which is comprised of a five-stranded β-barrel surrounded by two short α-helices. Furthermore, we revealed a non-specific DNA binding pattern of TbEsa1 Tudor domain. However, TbEsa1 Tudor domain showed no methyl-histone binding ability, due to the absence of key aromatic residues forming a conserved aromatic cage.
必需的 SAS2 相关乙酰转移酶 1(Esa1)作为 MYST 家族的乙酰转移酶,对于细胞周期和转录调控是不可或缺的。Tudor 结构域由 60 个氨基酸组成,属于 Royal 家族,作为与甲基化组蛋白和/或 DNA 相互作用的模块。尽管 Tudor 结构域在高等真核生物中得到了广泛研究,但在引起人类昏睡病和撒哈拉以南非洲牛的 nagana 的原生动物单细胞寄生虫——布氏锥虫(T. brucei)中,其结构和功能仍不清楚。在这里,我们通过 X 射线晶体学确定了来自 T. brucei 的 TbEsa1 假定的 Tudor 结构域的高分辨率结构。TbEsa1 Tudor 结构域采用保守的 Tudor 样折叠,由一个五链β桶组成,周围环绕着两个短的α螺旋。此外,我们揭示了 TbEsa1 Tudor 结构域的非特异性 DNA 结合模式。然而,由于缺乏形成保守的芳香族笼的关键芳香族残基,TbEsa1 Tudor 结构域没有甲基化组蛋白结合能力。