Department of Physiological Chemistry, Division of Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
FASEB J. 2010 Apr;24(4):981-93. doi: 10.1096/fj.09-136259. Epub 2009 Nov 25.
The family of ubiquitin-conjugating (E2) enzymes is characterized by the presence of a highly conserved ubiquitin-conjugating (UBC) domain. These domains accommodate the ATP-activated ubiquitin (Ub) or ubiquitin-like (UBL) protein via a covalently linked thioester onto its active-site residue. E2 enzymes act via selective protein-protein interactions with the E1 and E3 enzymes and connect activation to covalent modification. By doing so, E2s differentiate effects on downstream substrates, either with a single Ub/UBL molecule or as a chain. While E3s are involved in substrate selection, E2s are the main determinants for selection of the lysine to construct ubiquitin chains, which thereby directly control the cellular fate of the substrate. In humans, 35 active E2 enzymes have been identified so far, while other eukaryotic genomes harbor 16 to 35 E2 family members. Some E2s possess N- and/or C-terminal extensions that mediate E2-specific processes. During the past two decades, strong support has led to the control of E2 enzymes in decisions concerning the life or death of a protein. Here, we summarize current knowledge and recent developments on E2 enzymes with respect to structural characteristics and functions. From this we propose a shell-like model to rationalize the selectivity of these key enzymes in directing Ub/UBL-conjugation pathways.-Van Wijk, S. J. L., Timmers, H. T. M. The family of ubiquitin-conjugating enzymes (E2s): deciding between life and death of proteins.
泛素结合酶（E2）家族的特征是存在高度保守的泛素结合（UBC）结构域。这些结构域通过共价连接的硫酯键将活化的泛素（Ub）或泛素样（UBL）蛋白容纳在其活性位点残基上。E2 酶通过与 E1 和 E3 酶的选择性蛋白-蛋白相互作用发挥作用，并将激活与共价修饰连接起来。通过这种方式，E2 酶对下游底物的作用有两种方式：一种是用单个 Ub/UBL 分子，另一种是用链的方式。虽然 E3 酶参与了底物的选择，但 E2 酶是选择赖氨酸构建泛素链的主要决定因素，从而直接控制底物的细胞命运。到目前为止，在人类中已经鉴定出 35 种活跃的 E2 酶，而其他真核生物基因组则含有 16 到 35 种 E2 家族成员。一些 E2 酶具有 N-和/或 C-末端延伸，介导 E2 特异性过程。在过去的二十年中，强有力的证据表明 E2 酶在决定蛋白质的生死方面发挥了控制作用。在这里，我们总结了 E2 酶在结构特征和功能方面的最新知识和最新进展。在此基础上，我们提出了一个壳状模型，以合理化这些关键酶在指导 Ub/UBL 连接途径方面的选择性。
