Huai Qing, Sun Yingjie, Wang Huanchen, Chin Lih Shen, Li Lian, Robinson Howard, Ke Hengming
Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599-7260, USA.
FEBS Lett. 2003 Aug 14;549(1-3):171-5. doi: 10.1016/s0014-5793(03)00764-6.
DJ-1 is a protein involved in multiple physiological processes, including cancer, Parkinson's disease, and male fertility. It is unknown how DJ-1 functions in the apparently different systems. The crystal structure of DJ-1 at 1.6 A resolution shows that DJ-1 is a helix-strand-helix sandwich and forms a dimer. The DJ-1 structure is similar to the members of the intracellular protease PfpI family. However, the catalytic triad of Cys-His-Glu is not strictly conserved in DJ-1, implying that DJ-1 has a different catalytic mechanism if it acts as a protease or DJ-1 serves as a regulatory protein in the physiological processes. The structure shows that Leu166 positions in the middle of a helix and thus predicts that the L166P mutation will bend the helix and impact the dimerization of DJ-1. As a result, the conformational changes may diminish the DJ-1 binding with its partner, leading to the familial Parkinson's disease caused by the single L166P mutation.
DJ-1是一种参与多种生理过程的蛋白质，包括癌症、帕金森病和男性生育能力。目前尚不清楚DJ-1在这些明显不同的系统中是如何发挥作用的。分辨率为1.6埃的DJ-1晶体结构表明，DJ-1是一种螺旋-链-螺旋夹心结构，并形成二聚体。DJ-1的结构与细胞内蛋白酶PfpI家族的成员相似。然而，半胱氨酸-组氨酸-谷氨酸的催化三联体在DJ-1中并不严格保守，这意味着如果DJ-1作为蛋白酶起作用，其催化机制不同，或者DJ-1在生理过程中作为调节蛋白发挥作用。该结构表明，亮氨酸166位于一个螺旋的中间，因此预测L166P突变将使螺旋弯曲并影响DJ-1的二聚化。结果，构象变化可能会减少DJ-1与其伴侣的结合，导致由单一L166P突变引起的家族性帕金森病。
