Family-wide analysis of poly(ADP-ribose) polymerase activity.

Family-wide analysis of poly(ADP-ribose) polymerase activity.
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聚(ADP-核糖)聚合酶活性的家庭范围分析。

DOI:
10.1038/ncomms5426
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发表时间:
2014-07-21
影响因子:
16.6
通讯作者:
Chang, Paul
Chang, Paul
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Vyas, Sejal;Matic, Ivan;Uchima, Lilen;Rood, Jenny;Zaja, Roko;Hay, Ronald T.;Ahel, Ivan;Chang, Paul

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聚(ADP-核糖)聚合酶(PARP)蛋白家族以NAD+为底物对靶蛋白进行ADP-核糖(ADPr)修饰。根据三个NAD+配位氨基酸的组成,H-Y-E基序,每个PARP被预测产生多(ADP-核糖)(PAR)或单(ADP-核糖)(MAR)。然而,每个PARP的反应产物还没有明确的定义,是一个重要的优先事项,因为PAR和MAR通过不同的机制发挥作用。在这里,我们证明了大多数PAP产生MAR,而不是PAR,并证明H-Y-E基序不是PARP活性的唯一指标。我们确定了七个PARP上的自化位点,并证明了MAR和PAR生成的PARP可以修饰相似的氨基酸,这表明限制PARP合成MAR的序列和结构限制并不限制它们修改典型氨基酸靶标的能力。此外,我们发现半胱氨酸是PAPS上ADP-核糖化的新的氨基酸靶标。
The poly(ADP-ribose) polymerase (PARP) protein family generates ADP-ribose (ADPr) modifications onto target proteins using NAD+ as substrate. Based on the composition of three NAD+ coordinating amino acids, the H-Y-E motif, each PARP is predicted to generate either poly(ADP-ribose) (PAR) or mono(ADP-ribose) (MAR). However, the reaction product of each PARP has not been clearly defined, and is an important priority since PAR and MAR function via distinct mechanisms. Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. We identify automodification sites on seven PARPs, and demonstrate that MAR and PAR generating PARPs modify similar amino acids, suggesting that the sequence and structural constraints limiting PARPs to MAR synthesis do not limit their ability to modify canonical amino acid targets. In addition, we identify cysteine as a novel amino acid target for ADP-ribosylation on PARPs.
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