7EP1

Crystal structure of ZYG11B bound to GFLH degron

Summary for 7EP1

• Entry DOI: 10.2210/pdb7ep1/pdb
• Descriptor: Protein zyg-11 homolog B (2 entities in total)
• Functional Keywords: e3 ligase, ligase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 57099.30

Authors

Yan, X.,Li, Y. (deposition date: 2021-04-26, release date: 2021-07-14, Last modification date: 2023-11-29)

Primary citation

Yan, X.,Li, Y.,Wang, G.,Zhou, Z.,Song, G.,Feng, Q.,Zhao, Y.,Mi, W.,Ma, Z.,Dong, C.
Molecular basis for recognition of Gly/N-degrons by CRL2 ZYG11B and CRL2 ZER1 .
Mol.Cell, 81:3262-3274.e3, 2021

PubMed Abstract: N-degron pathways are a set of proteolytic systems that target the N-terminal destabilizing residues of substrates for proteasomal degradation. Recently, the Gly/N-degron pathway has been identified as a new branch of the N-degron pathway. The N-terminal glycine degron (Gly/N-degron) is recognized by ZYG11B and ZER1, the substrate receptors of the Cullin 2-RING E3 ubiquitin ligase (CRL2). Here we present the crystal structures of ZYG11B and ZER1 bound to various Gly/N-degrons. The structures reveal that ZYG11B and ZER1 utilize their armadillo (ARM) repeats forming a deep and narrow cavity to engage mainly the first four residues of Gly/N-degrons. The α-amino group of the Gly/N-degron is accommodated in an acidic pocket by five conserved hydrogen bonds. These structures, together with biochemical studies, decipher the molecular basis for the specific recognition of the Gly/N-degron by ZYG11B and ZER1, providing key information for future structure-based chemical probe design.

PubMed: 34214466
DOI: 10.1016/j.molcel.2021.06.010

Experimental method

X-RAY DIFFRACTION (1.852 Å)