Solution structure of a zinc-finger domain that binds to poly-ADP-ribose
Solution structure of a zinc-finger domain that binds to poly-ADP-ribose
复制标题
DOI：
10.1111/j.1365-2443.2009.01369.x
复制
发表时间：
2010-02-01
期刊：
影响因子：
2.1
通讯作者：
Shirakawa, Masahiro
中科院分区：
文献类型：
--
作者：
Isogai, Shin;Kanno, Shin-Ichiro;Shirakawa, Masahiro
Poly-ADP-核糖化是一种独特的翻译后修饰，控制着各种核事件，如DNA单链断裂的修复。最近，含有聚腺苷二磷酸核糖(PADPr)结合锌指(PBZ)结构域的蛋白质被发现是一种新的AP内切酶，参与细胞周期检查点。在这里，我们使用核磁共振技术确定了果蝇黑腹果蝇CG1218-PA的PBZ结构域的三维结构。该结构域在S构型中折叠成C2H2型锌指结构，在与锌配位的半胱氨酸和组氨酸残基之间包含一个特征环。这与其他C2H2型锌指的结构不同。当pADPr从CG1218-PA与PBZ结构域结合时，以及人与FHA(叉头相关)和无名指(CHFR)的检查点结合时发生的核磁共振信号变化表明，PBZ结构域之间相对保守的表面可能是pADPr的主要界面。
Poly-ADP-ribosylation is a unique post-translational modification that controls various nuclear events such as repair of DNA single-strand breaks. Recently, the protein containing the poly-ADP-ribose (pADPr)-binding zinc-finger (PBZ) domain was shown to be a novel AP endonuclease and involved in a cell cycle checkpoint. Here, we determined the three-dimensional structure of the PBZ domain from Drosophila melanogaster CG1218-PA using NMR spectroscopy. The domain folds into a C2H2-type zinc-finger structure in an S configuration, containing a characteristic loop between the zinc-coordinating cysteine and histidine residues. This is distinct from the structure of other C2H2-type zinc fingers. NMR signal changes that occur when pADPr binds to the PBZ domains from CG1218-PA and human checkpoint with FHA (forkhead-associated) and ring finger (CHFR) and mutagenesis suggest that a surface relatively well conserved among PBZ domains may serve as a major interface with pADPr.