ADP-ribosylation of arginine.
ADP-ribosylation of arginine.
复制标题
精氨酸的ADP-核糖基化。
DOI：
10.1007/s00726-010-0676-2
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发表时间：
2011-07
期刊：
影响因子：
3.5
通讯作者：
Haag, Friedrich
中科院分区：
文献类型：
--
作者：
Laing, Sabrina;Unger, Mandy;Koch-Nolte, Friedrich;Haag, Friedrich
关键词：
精氨酸腺苷-5‘-二磷酸核糖基化(ADP-核糖化)是一种酶催化的、潜在可逆的翻译后修饰，其中ADP-核糖部分从NAD+转移到精氨酸的胍基部分。ADP-核糖的大小约为5个氨基酸残基，大小为540kDa。与精氨酸相反，精氨酸在中性pH下带正电荷，而ADP-核糖携带两个带负电荷的磷酸部分。因此，精氨酸ADP-核糖化导致目标蛋白的ADP-核糖化位点的大小和化学性质发生显著变化。通常，这会导致目标蛋白与结合伙伴相互作用的空间干扰，例如毒素催化的肌动蛋白在R177位的ADP-核糖化作用会立体地阻止肌动蛋白聚合。对于核苷酸门控的P2X7离子通道，配体结合位点附近的R125处的ADP-核糖基化会导致通道门控。精氨酸特异的腺苷二磷酸核糖基转移酶(ARTS)带有一个特有的R-S-EXE基序，它与催化其他氨基酸侧链、脱氧核糖核酸或小分子的腺苷二磷酸核糖化的结构相关酶不同。精氨酸专一性的ADP-核糖化可以被小分子精氨酸类似物所抑制，这些小分子精氨酸类似物本身可以作为精氨酸专一性ART的靶点。ADP-核糖精氨酸特异性水解酶(ARHS)可以通过水解性去除整个ADP-核糖部分来恢复靶蛋白的功能。在某些情况下，ADP-核糖精氨酸被加工成二级翻译后修饰，例如磷酸核糖精氨酸或鸟氨酸。本文综述了精氨酸特异性ADP-核糖化的研究现状，重点介绍了精氨酸特异性ADP-核糖化的检测方法、生物学意义、修饰和逆转的酶类，并对该领域的研究前景进行了展望。
Arginine adenosine-5′-diphosphoribosylation (ADP-ribosylation) is an enzyme-catalyzed, potentially reversible posttranslational modification, in which the ADP-ribose moiety is transferred from NAD+ to the guanidino moiety of arginine. At 540 Da, ADP-ribose has the size of approximately five amino acid residues. In contrast to arginine, which, at neutral pH, is positively charged, ADP-ribose carries two negatively charged phosphate moieties. Arginine ADP-ribosylation, thus, causes a notable change in size and chemical property at the ADP-ribosylation site of the target protein. Often, this causes steric interference of the interaction of the target protein with binding partners, e.g. toxin-catalyzed ADP-ribosylation of actin at R177 sterically blocks actin polymerization. In case of the nucleotide-gated P2X7 ion channel, ADP-ribosylation at R125 in the vicinity of the ligand-binding site causes channel gating. Arginine-specific ADP-ribosyltransferases (ARTs) carry a characteristic R-S-EXE motif that distinguishes these enzymes from structurally related enzymes which catalyze ADP-ribosylation of other amino acid side chains, DNA, or small molecules. Arginine-specific ADP-ribosylation can be inhibited by small molecule arginine analogues such as agmatine or meta-iodobenzylguanidine (MIBG), which themselves can serve as targets for arginine-specific ARTs. ADP-ribosylarginine specific hydrolases (ARHs) can restore target protein function by hydrolytic removal of the entire ADP-ribose moiety. In some cases, ADP-ribosylarginine is processed into secondary posttranslational modifications, e.g. phosphoribosylarginine or ornithine. This review summarizes current knowledge on arginine-specific ADP-ribosylation, focussing on the methods available for its detection, its biological consequences, and the enzymes responsible for this modification and its reversal, and discusses future perspectives for research in this field.
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