不同的HECT结构域泛素连接酶采用不同的多聚泛素链合成机制。
Different HECT domain ubiquitin ligases employ distinct mechanisms of polyubiquitin chain synthesis.
作者信息
Wang Min, Pickart Cecile M
机构信息
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
出版信息
EMBO J. 2005 Dec 21;24(24):4324-33. doi: 10.1038/sj.emboj.7600895. Epub 2005 Dec 8.
Individual ubiquitin (Ub)-protein ligases (E3s) cooperate with specific Ub-conjugating enzymes (E2s) to modify cognate substrates with polyubiquitin chains. E3s belonging to the Really Interesting New Gene (RING) and Homologous to E6-Associated Protein (E6AP) C-Terminus (HECT) domain families utilize distinct molecular mechanisms. In particular, HECT E3s, but not RING E3s, form a thiol ester with Ub before transferring Ub to the substrate lysine. Here we report that different HECT domain E3s can employ distinct mechanisms of polyubiquitin chain synthesis. We show that E6AP builds up a K48-linked chain on its HECT cysteine residue, while KIAA10 builds up K48- and K29-linked chains as free entities. A small region near the N-terminus of the conserved HECT domain helps to bring about this functional distinction. Thus, a given HECT domain can specify both the linkage of a polyubiquitin chain and the mechanism of its assembly.
单个泛素（Ub）-蛋白连接酶（E3）与特定的Ub结合酶（E2）协同作用，用多聚泛素链修饰同源底物。属于真正有趣的新基因（RING）和与E6相关蛋白（E6AP）C末端同源（HECT）结构域家族的E3利用不同的分子机制。特别是，HECT E3而非RING E3在将Ub转移到底物赖氨酸之前会与Ub形成硫酯。在此我们报道，不同的HECT结构域E3可以采用不同的多聚泛素链合成机制。我们发现E6AP在其HECT半胱氨酸残基上形成K48连接的链，而KIAA10则以游离实体形式形成K48和K29连接的链。保守HECT结构域N末端附近的一个小区域有助于实现这种功能差异。因此，给定的HECT结构域既可以指定多聚泛素链的连接方式，也可以指定其组装机制。
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