Verdecia Mark A, Joazeiro Claudio A P, Wells Nicholas J, Ferrer Jean-Luc, Bowman Marianne E, Hunter Tony, Noel Joseph P
Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Mol Cell. 2003 Jan;11(1):249-59. doi: 10.1016/s1097-2765(02)00774-8.
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.
泛素连接酶（E3）选择要进行泛素化修饰的蛋白质，这种修饰可引导靶蛋白的亚细胞运输改变和/或降解。HECT结构域E3连接酶不仅能识别其蛋白质底物，还能直接催化泛素与底物的连接。人泛素连接酶WWP1/AIP5的HECT结构域的晶体结构与人类泛素连接酶E6AP的HECT结构域一样，保持双叶结构。虽然WWP1的单个N叶和C叶与E6AP的折叠非常相似，但由于围绕连接N叶和C叶的多肽铰链的旋转，两个叶彼此之间的组织方式与E6AP不同。突变分析表明，围绕该铰链区域旋转所实现的一系列构象对于催化活性至关重要。
