7CNC

cystal structure of human ERH in complex with DGCR8

Summary for 7CNC

• Entry DOI: 10.2210/pdb7cnc/pdb
• Descriptor: Enhancer of rudimentary homolog, Microprocessor complex subunit DGCR8 (3 entities in total)
• Functional Keywords: protein-protein interaction, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 16807.20

Authors

Li, F.,Shen, S. (deposition date: 2020-07-30, release date: 2020-10-28, Last modification date: 2023-11-29)

Primary citation

Kwon, S.C.,Jang, H.,Shen, S.,Baek, S.C.,Kim, K.,Yang, J.,Kim, J.,Kim, J.S.,Wang, S.,Shi, Y.,Li, F.,Kim, V.N.
ERH facilitates microRNA maturation through the interaction with the N-terminus of DGCR8.
Nucleic Acids Res., 48:11097-11112, 2020

PubMed Abstract: The microprocessor complex cleaves the primary transcript of microRNA (pri-miRNA) to initiate miRNA maturation. Microprocessor is known to consist of RNase III DROSHA and dsRNA-binding DGCR8. Here, we identify Enhancer of Rudimentary Homolog (ERH) as a new component of Microprocessor. Through a crystal structure and biochemical experiments, we reveal that ERH uses its hydrophobic groove to bind to a conserved region in the N-terminus of DGCR8, in a 2:2 stoichiometry. Knock-down of ERH or deletion of the DGCR8 N-terminus results in a reduced processing of suboptimal pri-miRNAs in polycistronic miRNA clusters. ERH increases the processing of suboptimal pri-miR-451 in a manner dependent on its neighboring pri-miR-144. Thus, the ERH dimer may mediate 'cluster assistance' in which Microprocessor is loaded onto a poor substrate with help from a high-affinity substrate in the same cluster. Our study reveals a role of ERH in the miRNA biogenesis pathway.

PubMed: 33035348
DOI: 10.1093/nar/gkaa827

Experimental method

X-RAY DIFFRACTION (1.6 Å)