7XYU

Crystal structure of ZER1 bound to TFLH degron

7XYU の概要

• エントリーDOI: 10.2210/pdb7xyu/pdb
• 分子名称: Protein zer-1 homolog (2 entities in total)
• 機能のキーワード: e3, ligase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 116731.11

構造登録者

Dong, C.,Yan, X.,Li, Y. (登録日: 2022-06-02, 公開日: 2022-12-21, 最終更新日: 2023-11-29)

主引用文献

Li, Y.,Zhao, Y.,Yan, X.,Ye, C.,Weirich, S.,Zhang, B.,Wang, X.,Song, L.,Jiang, C.,Jeltsch, A.,Dong, C.,Mi, W.
CRL2 ZER1/ZYG11B recognizes small N-terminal residues for degradation.
Nat Commun, 13:7636-7636, 2022

PubMed Abstract: N-degron pathway plays an important role in the protein quality control and maintenance of cellular protein homeostasis. ZER1 and ZYG11B, the substrate receptors of the Cullin 2-RING E3 ubiquitin ligase (CRL2), recognize N-terminal (Nt) glycine degrons and participate in the Nt-myristoylation quality control through the Gly/N-degron pathway. Here we show that ZER1 and ZYG11B can also recognize small Nt-residues other than glycine. Specifically, ZER1 binds better to Nt-Ser, -Ala, -Thr and -Cys than to -Gly, while ZYG11B prefers Nt-Gly but also has the capacity to recognize Nt-Ser, -Ala and -Cys in vitro. We found that Nt-Ser, -Ala and -Cys undergo Nt-acetylation catalyzed by Nt-acetyltransferase (NAT), thereby shielding them from recognition by ZER1/ZYG11B in cells. Instead, ZER1/ZYG11B readily targets a selection of small Nt-residues lacking Nt-acetylation for degradation in NAT-deficient cells, implicating its role in the Nt-acetylation quality control. Furthermore, we present the crystal structures of ZER1 and ZYG11B bound to various small Nt-residues and uncover the molecular mechanism of non-acetylated substrate recognition by ZER1 and ZYG11B.

PubMed: 36496439
DOI: 10.1038/s41467-022-35169-6

実験手法

X-RAY DIFFRACTION (2.7 Å)