Shin Jin Seok, Park Si Hoon, Kim Leehyeon, Heo Jiwon, Song Hyun Kyu
Department of Life Sciences, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, South Korea.
Department of Life Sciences, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, South Korea.
Biochem Biophys Res Commun. 2021 Dec 10;582:86-92. doi: 10.1016/j.bbrc.2021.10.007. Epub 2021 Oct 6.
The cellular glucose level has to be tightly regulated by a variety of cellular processes. One of them is the degradation of gluconeogenic enzymes such as Fbp1, Icl1, Mdh2, and Pck1 by GID (glucose-induced degradation deficient) E3 ubiquitin ligase. The Gid4 component of the GID ligase complex is responsible for recognizing the N-terminal proline residue of the target substrates under normal conditions. However, an alternative N-recognin Gid10 controls the degradation process under stressed conditions. Although Gid10 shares a high sequence similarity with Gid4, their substrate specificities are quite different. Here, we report the structure of Gid10 from Saccharomyces cerevisiae in complex with Pro/N-degron, Pro-Tyr-Ile-Thr, which is almost identical to the sequence of the natural substrate Art2. Although Gid10 shares many structural features with the Gid4 protein from yeast and humans, the current structure explains the unique structural difference for the preference of bulky hydrophobic residue at the second position of Pro/N-degron. Therefore, this study provides a fundamental basis for understanding of the structural diversity and substrate specificity of recognition components in the GID E3 ligase complex involved in the Pro/N-degron pathway.
细胞内的葡萄糖水平必须通过多种细胞过程进行严格调控。其中之一是葡萄糖诱导降解缺陷型（GID）E3泛素连接酶对诸如Fbp1、Icl1、Mdh2和Pck1等糖异生酶的降解。在正常条件下，GID连接酶复合物的Gid4组分负责识别靶底物的N端脯氨酸残基。然而，另一种N识别蛋白Gid10在应激条件下控制降解过程。尽管Gid10与Gid4具有高度的序列相似性，但其底物特异性却大不相同。在此，我们报道了酿酒酵母中与Pro/N-降解子Pro-Tyr-Ile-Thr形成复合物的Gid10的结构，该序列与天然底物Art2的序列几乎相同。尽管Gid10与酵母和人类的Gid4蛋白具有许多结构特征，但目前的结构解释了Pro/N-降解子第二位偏好大体积疏水残基的独特结构差异。因此，本研究为理解参与Pro/N-降解子途径的GID E3连接酶复合物中识别组分的结构多样性和底物特异性提供了基础。
