Centre for Structural Systems Biology (CSSB), Hamburg, Germany.
Institute of Complex Systems (ICS-6), Forschungszentrum Juelich, Juelich, Germany.
Cell Death Differ. 2017 Sep;24(9):1540-1547. doi: 10.1038/cdd.2017.76. Epub 2017 Jun 16.
Par-4 is a unique proapoptotic protein with the ability to induce apoptosis selectively in cancer cells. The X-ray crystal structure of the C-terminal domain of Par-4 (Par-4), which regulates its apoptotic function, was obtained by MAD phasing. Par-4 homodimerizes by forming a parallel coiled-coil structure. The N-terminal half of Par-4 contains the homodimerization subdomain. This structure includes a nuclear export signal (Par-4) sequence, which is masked upon dimerization indicating a potential mechanism for nuclear localization. The heteromeric-interaction models specifically showed that charge interaction is an important factor in the stability of heteromers of the C-terminal leucine zipper subdomain of Par-4 (Par-4). These heteromer models also displayed NES masking capacity and therefore the ability to influence intracellular localization.
Par-4 是一种独特的促凋亡蛋白，能够选择性地诱导癌细胞凋亡。通过 MAD 相位法获得了调控其凋亡功能的 Par-4（Par-4）C 端结构域的 X 射线晶体结构。Par-4 通过形成平行的卷曲螺旋结构进行同源二聚化。Par-4 的 N 端包含同源二聚化亚结构域。该结构包含一个核输出信号（Par-4）序列，该序列在二聚化时被掩盖，表明存在一种潜在的核定位机制。杂相互作用模型特别表明，电荷相互作用是 Par-4（Par-4）C 端亮氨酸拉链亚结构域异源二聚体稳定性的重要因素。这些异源二聚体模型还显示了 NES 掩蔽能力，因此能够影响细胞内定位。
