7XYX

Crystal structure of ZYG11B bound to CFLH degron

Summary for 7XYX

• Entry DOI: 10.2210/pdb7xyx/pdb
• Descriptor: Protein zyg-11 homolog B (2 entities in total)
• Functional Keywords: e3, ligase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 57191.48

Authors

Dong, C.,Yan, X.,Li, Y. (deposition date: 2022-06-02, release date: 2022-12-21, Last modification date: 2023-11-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.87 Å)