蛋白质泛素化修饰有着重要的生物学功能。在泛素化修饰过程中，泛素相互之间可以连接在一起形成泛素链。在泛素上有7个赖氨酸残基，所有这7个赖氨酸都可以被用来合成泛素链，而且不同连接方式的泛素链具有不同的功能。其中Lys48连接的泛素链是研究最为充分的连接方式之一，其主要介导蛋白质的降解，但是哺乳动物体内Lys48 连接的泛素链合成机制尚清楚。

　　李卫研究组利用离体重建的Ube2g2和gp78泛素化修饰体系，研究发现在该体系中Ube2g2的二聚化促成泛素链的非对称合成；结合Ub的Ube2g2分子间亲和力增加；供体ube2g2分子与受体Ub之间存在离子互作，并且正是这种互作决定了泛素链lys48的连接方式；进一步研究发现，ube2g2催化泛素化合成机制在内质网降解途径中发挥着重要作用，从而系统地揭示了生物体内Ube2g2催化lys48连接的泛素链形成的分子机制。

　　以上研究成果于12月23日在线发表于EMBO J.。该研究工作得到了国家自然科学基金，中国科学院****和科技部发育与生殖重大研究计划的支持的支持。

原文摘要：

Dimeric Ube2g2 simultaneously engages donor and acceptor ubiquitins to form Lys48‐linked ubiquitin chains

Abstract
Cellular adaptation to proteotoxic stress at the endoplasmic reticulum (ER) depends on Lys48‐linked polyubiquitination by ER‐associated ubiquitin ligases (E3s) and subsequent elimination of ubiquitinated retrotranslocation products by the proteasome. The ER‐associated E3 gp78 ubiquitinates misfolded proteins by transferring preformed Lys48‐linked ubiquitin chains from the cognate E2 Ube2g2 to substrates. Here we demonstrate that Ube2g2 synthesizes linkage specific ubiquitin chains by forming an unprecedented homodimer: The dimerization of Ube2g2, mediated primarily by electrostatic interactions between two Ube2g2s, is also facilitated by the charged ubiquitin molecules. Mutagenesis studies show that Ube2g2 dimerization is required for ER‐associated degradation (ERAD). In addition to E2 dimerization, we show that a highly conserved arginine residue in the donor Ube2g2 senses the presence of an aspartate in the acceptor ubiquitin to position only Lys48 of ubiquitin in proximity to the donor E2 active site. These results reveal an unanticipated mode of E2 self‐association that allows the E2 to effectively engage two ubiquitins to specifically synthesize Lys48‐linked ubiquitin chains.