C-terminal glutamine acts as a C-degron targeted by E3 ubiquitin ligase TRIM7
Yawei Ru, Xiaojie Yan, Bing Zhang, Lili Song, Qiqi Feng, Chen Ye, Zhili Zhou, Zhenzhen Yang, Yao Li, Zhenjian Zhang, Qianqian Li, Wenyi Mi, Dong Cheng
Abstract
The exposed N-terminal or C-terminal residues of proteins can act, in cognate sequence contexts, as degradation signals (degrons) that are targeted by specific E3 ubiquitin ligases for proteasome-dependent degradation by N -degron or C-degron pathways. Here, we discovered a distinct C-degron pathway, termed the Gln/C-degron pathway, in which the B30.2 domain of E3 ubiquitin ligase TRIM7 (TRIM7 B30.2 ) mediates the recognition of proteins bearing a C-terminal glutamine. By determining crystal structures of TRIM7 B30.2 in complexes with various peptides, we show that TRIM7 B30.2 forms a positively charged binding pocket to engage the “U”-shaped Gln/C-degron. The four C-terminal residues of a substrate play an important role in C-degron recognition, with C-terminal glutamine as the principal determinant. In vitro biochemical and cellular experiments were used to further analyze the substrate specificity and selective degradation of the Gln/C-degron by TRIM7.