7X39

Structure of CIZ1 bound ERH

Summary for 7X39

• Entry DOI: 10.2210/pdb7x39/pdb
• Descriptor: Enhancer of rudimentary homolog,Cip1-interacting zinc finger protein (1 entity in total)
• Functional Keywords: erh, ciz1, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 68800.49

Authors

Wang, X.,Xu, C. (deposition date: 2022-02-28, release date: 2022-08-31, Last modification date: 2023-11-29)

Primary citation

Wang, X.,Xie, H.,Zhu, Z.,Zhang, J.,Xu, C.
Molecular basis for the recognition of CIZ1 by ERH.
Febs J., 290:712-723, 2023

PubMed Abstract: Enhancer of rudimentary homologue (ERH), a small protein conserved in eukaryotes, is involved in a wide spectrum of cellular events, including cell cycle progression, piRNA biogenesis, miRNA maturation and gene expression. Human ERH is recruited to replication foci by CDKN1A-interacting zinc finger protein 1 (CIZ1), and plays an important role in cell growth control. However, the molecular basis for CIZ1 recognition by ERH remains unknown. By using GST pull-down experiment, we found that a fragment within CIZ1, upstream of its first zinc finger, is sufficient for binding to ERH. We solved the structure of CIZ1-bound ERH, in which the ERH dimer binds to two CIZ1 fragments to form a 2 : 2 heterotetramer. CIZ1 forms intermolecular antiparallel β-strands with ERH, and its binding surface on ERH is distinct from those of other known ERH-binding ligands. The ERH-CIZ1 interface was further validated by mutagenesis and binding experiments. Our structural study complemented by biochemistry experiments not only provides insights into a previously unidentified ligand-binding mode for ERH but also sheds light on the understanding of evolutionarily conserved roles for ERH orthologs.

PubMed: 36047590
DOI: 10.1111/febs.16611

Experimental method

X-RAY DIFFRACTION (2.85 Å)