E3连接酶Pirh2识别富含丙氨酸C端降解决定子的分子机制
Recognition of an Ala-rich C-degron by the E3 ligase Pirh2
Wang Xiaolu, Li Yao, Yan Xiaojie, Yang Qing, Zhang Bing, Zhang Ying, Yuan Xinxin, Jiang Chenhao, Chen Dongxing, Liu Quanyan, Liu Tong, Mi Wenyi, Yu Ying, Dong Cheng
Journal：Nature Communications
IF：16.6
DOI：10.1038/s41467-023-38173-6
PMID：37120596
Published：2023-04-29
research field：分子生物学细胞生物学蛋白质降解遗传学与基因组学内分泌与代谢
Abstract
The ribosome-associated quality-control (RQC) pathway degrades aberrant nascent polypeptides arising from ribosome stalling during translation. In mammals, the E3 ligase Pirh2 mediates the degradation of aberrant nascent polypeptides by targeting the C-terminal polyalanine degrons (polyAla/C-degrons). Here, we present the crystal structure of Pirh2 bound to the polyAla/C-degron, which shows that the N-terminal domain and the RING domain of Pirh2 form a narrow groove encapsulating the alanine residues of the polyAla/C-degron. Affinity measurements in vitro and global protein stability assays in cells further demonstrate that Pirh2 recognizes a C-terminal A/S-X-A-A motif for substrate degradation. Taken together, our study provides the molecular basis underlying polyAla/C-degron recognition by Pirh2 and expands the substrate recognition spectrum of Pirh2.
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