Cancer Research UK, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.
Rudjer Boskovic Institute, Bijenicka 54, Zagreb 10000, Croatia.
Biomolecules. 2012 Dec 21;3(1):1-17. doi: 10.3390/biom3010001.
Poly(ADP-ribosyl)ation is a post-translational protein modification involved in the regulation of important cellular functions including DNA repair, transcription, mitosis and apoptosis. The amount of poly(ADP-ribosyl)ation (PAR) in cells reflects the balance of synthesis, mediated by the PARP protein family, and degradation, which is catalyzed by a glycohydrolase, PARG. Many of the proteins mediating PAR metabolism possess specialised high affinity PAR-binding modules that allow the efficient sensing or processing of the PAR signal. The identification of four such PAR-binding modules and the characterization of a number of proteins utilising these elements during the last decade has provided important insights into how PAR regulates different cellular activities. The macrodomain represents a unique PAR-binding module which is, in some instances, known to possess enzymatic activity on ADP-ribose derivatives (in addition to PAR-binding). The most recently discovered example for this is the PARG protein, and several available PARG structures have provided an understanding into how the PARG macrodomain evolved into a major enzyme that maintains PAR homeostasis in living cells.
聚（ADP-核糖）化是一种翻译后蛋白质修饰，参与调节包括 DNA 修复、转录、有丝分裂和细胞凋亡在内的重要细胞功能。细胞中聚（ADP-核糖）化（PAR）的量反映了合成的平衡，由 PARP 蛋白家族介导，降解由糖基水解酶 PARG 催化。许多介导 PAR 代谢的蛋白质具有专门的高亲和力 PAR 结合模块，允许有效地感知或处理 PAR 信号。在过去十年中，已经鉴定出四个这样的 PAR 结合模块，并对利用这些元件的许多蛋白质进行了特征描述，这为 PAR 如何调节不同的细胞活动提供了重要的见解。宏结构域代表一种独特的 PAR 结合模块，在某些情况下，已知对 ADP-核糖衍生物具有酶活性（除 PAR 结合外）。最近发现的一个例子是 PARG 蛋白，并且已经有几个可用的 PARG 结构提供了对 PARG 宏结构域如何进化成维持活细胞中 PAR 动态平衡的主要酶的理解。
