Non-enzymatic synthesis of ubiquitin chains: Where chemistry makes a difference
Non-enzymatic synthesis of ubiquitin chains: Where chemistry makes a difference
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DOI：
10.1016/j.bmc.2013.02.004
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发表时间：
2013-06-15
影响因子：
3.5
通讯作者：
Brik, Ashraf
中科院分区：
文献类型：
--
作者：
Hemantha, Hosahalli P.;Brik, Ashraf
泛素化是真核细胞中一种非常重要的翻译后修饰，目的蛋白通过异肽键与泛素或泛素链结合，引发蛋白酶体降解等多种细胞事件。在分子水平上对泛素信号的严格研究需要同质的自由形式的泛素链样本或足够数量的锚定在蛋白质底物上的泛素链样本。泛素链在连接类型方面的复杂性(由于泛素中存在七个赖氨酸)使得它们很难通过酶法制备。更具挑战性的是将这些链连接到选定位置的蛋白质靶标上。这一不足正在被新的化学工具的最新发展所填补，这些工具为结构和功能研究提供了对合成的原子水平控制。这些新出现的化学方法将在这篇小型综述中讨论，重点是泛素链的制备，以帮助正在进行的努力了解它们在泛素信号中的作用。(C)2013爱思唯尔有限公司。保留所有权利。
Ubiquitination is a highly important posttranslational modification in eukaryotic cells where a target protein is conjugated to ubiquitin or a chain of ubiquitins via an isopeptide bond to trigger various cellular events such as proteasomal degradation. Rigorous investigations of the ubiquitin signal at the molecular level require homogeneous samples of ubiquitin chains in their free form or as anchored to a protein substrate in adequate quantities. The complexity of ubiquitin chains in terms of linkage types (owing to presence of seven Lys in ubiquitin) makes them difficult to prepare via enzymatic methods. Even more challenging is the attachment of these chains to a protein target at a selected site. This dearth is being filled by the recent developments of novel chemical tools that offer atomic level control over the synthesis for structural and functional studies. These emerging chemical approaches are discussed in this mini-review with focus on the preparation of ubiquitin chains to aid the ongoing efforts in understanding their role in the ubiquitin signal. (C) 2013 Elsevier Ltd. All rights reserved.