Structure of the human p53 core domain in the absence of DNA
Structure of the human p53 core domain in the absence of DNA
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DOI：
10.1107/s0907444906048499
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发表时间：
2007-03-01
影响因子：
2.2
通讯作者：
Luecke, Hartmut
中科院分区：
文献类型：
--
作者：
Wang, Ying;Rosengarth, Anja;Luecke, Hartmut
肿瘤抑制蛋白 p53 在收到适当信号时触发 DNA 修复、细胞周期停滞和细胞凋亡，从而在细胞周期调节中发挥关键作用。 p53 具有转录因子的经典结构，包括氨基末端反式激活结构域、核心 DNA 结合结构域以及羧基末端四聚化和调节结构域。 p53 核心结构域的晶体结构（包括从残基 96 到残基 289 的氨基酸）已在不存在 DNA 的情况下以 2.05 埃的分辨率测定。晶体在新的单斜空间群（P2（1））中生长，晶胞参数a = 68.91，b = 69.36，c = 84.18埃，β = 90.11度。该结构通过分子置换得到解析，并已精炼至最终 R 因子为 20.9%（无 R = 24.6%）。最终模型包含不对称单元中的四个分子、四个锌离子和 389 个水分子。非晶体四聚体显示出与其他 p53 晶体中不同的蛋白质接触，从而引发了 p53 在结合其靶 DNA 时如何排列为四聚体的问题。
The tumor suppressor protein p53 plays a key role in cell-cycle regulation by triggering DNA repair, cell-cycle arrest and apoptosis when the appropriate signal is received. p53 has the classic architecture of a transcription factor, with an amino-terminal transactivation domain, a core DNA-binding domain and carboxy-terminal tetramerization and regulatory domains. The crystal structure of the p53 core domain, which includes the amino acids from residue 96 to residue 289, has been determined in the absence of DNA to a resolution of 2.05 angstrom. Crystals grew in a new monoclinic space group (P2(1)), with unit-cell parameters a = 68.91, b= 69.36, c= 84.18 angstrom, beta = 90.11 degrees. The structure was solved by molecular replacement and has been refined to a final R factor of 20.9% (R-free = 24.6%). The final model contains four molecules in the asymmetric unit with four zinc ions and 389 water molecules. The noncrystallographic tetramers display different protein contacts from those in other p53 crystals, giving rise to the question of how p53 arranges as a tetramer when it binds its target DNA.