Human lysosomal DNase IIα contains two requisite PLD-signature (HxK) motifs:: Evidence for a pseudodimeric structure of the active enzyme species
Human lysosomal DNase IIα contains two requisite PLD-signature (HxK) motifs:: Evidence for a pseudodimeric structure of the active enzyme species
复制标题
DOI：
10.1110/ps.062535307
复制
发表时间：
2007-01-01
期刊：
影响因子：
8
通讯作者：
Meiss, Gregor
中科院分区：
文献类型：
--
作者：
Schaefer, Patrick;Cymerman, Iwona A.;Meiss, Gregor
在高等真核生物中，溶酶体DNA酶II α对于DNA废物去除和辅助凋亡DNA片段化是必需的。尽管这种酶的关键作用，很少有人知道它的结构与功能的关系。在这里，使用突变和生化分析来表征哺乳动物细胞中表达的人DNA酶IIa变体。所得的数据强烈支持的假设，该酶是一个单体磷脂酶D-家族成员的假二聚体蛋白质折叠。根据我们的研究结果，DNase IIa在N-和C-末端亚结构域中分别含有两个必需的PLD-签名基序（（HTK 115）-H-113和（HSK 297）-H-295），它们一起形成单个活性位点。基于这些数据，我们提出了一个实验验证的DNA酶IIa的结构模型。
Lysosomal DNase II alpha is essential for DNA waste removal and auxiliary apoptotic DNA fragmentation in higher eukaryotes. Despite the key role of this enzyme, little is known about its structure-function relationships. Here, mutational and biochemical analyses were used to characterize human DNase IIa variants expressed in mammalian cells. The resulting data strongly support the hypothesis that the enzyme is a monomeric phospholipase D-family member with a pseudodimeric protein fold. According to our results, DNase IIa contains two requisite PLD-signature motifs ((HTK115)-H-113 and (HSK297)-H-295) in the N- and C-terminal subdomains, respectively, that together form a single active site. Based on these data, we present an experimentally validated structural model of DNase IIa.