Conformational flexibility underlies ubiquitin ligation mediated by the WWP1HECT domain E3 ligase
Conformational flexibility underlies ubiquitin ligation mediated by the WWP1HECT domain E3 ligase
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DOI：
10.1016/s1097-2765(02)00774-8
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发表时间：
2003-01-01
期刊：
影响因子：
16
通讯作者：
Noel, JP
中科院分区：
文献类型：
--
作者：
Verdecia, MA;Joazeiro, CAP;Noel, JP
泛素连接酶（E3）选择蛋白质进行泛素化，这是一种指导改变亚细胞运输和/或目标蛋白降解的修饰。HECT结构域E3连接酶不仅识别并直接催化泛素与其蛋白底物的连接。人泛素连接酶WWP1/AIP5的HECT结构域晶体结构与人泛素连接酶E6AP的HECT结构域类似，维持双叶结构。虽然WWP1的单个N和C叶瓣与E6AP的褶皱非常相似，但由于连接N和C叶瓣的多肽铰链旋转，这两个叶瓣之间的相对组织与E6AP不同。突变分析表明，围绕该铰链区域旋转获得的一系列构象对催化活性至关重要。
Ubiquitin ligases (E3) select proteins for ubiquitylation, a modification that directs altered subcellular trafficking and/or degradation of the target protein. HECT domain E3 ligases not only recognize, but also directly catalyze, ligation of ubiquitin to their protein substrates. The crystal structure of the HECT domain of the human ubiquitin ligase WWP1/AIP5 maintains a two-lobed structure like the HECT domain of the human ubiquitin ligase E6AP. While the individual N and C lobes of WWP1 possess very similar folds to those of E6AP, the organization of the two lobes relative to one another is different from E6AP due to a rotation about a polypeptide hinge linking the N and C lobes. Mutational analyses suggest that a range of conformations achieved by rotation about this hinge region is essential for catalytic activity.