3LE4

Crystal structure of the DGCR8 dimerization domain

Summary for 3LE4

• Entry DOI: 10.2210/pdb3le4/pdb
• Descriptor: Microprocessor complex subunit DGCR8 (2 entities in total)
• Functional Keywords: ww motif, dimerization, 3d domain swapping, heme binding, microrna processing, heme, iron, metal-binding, nucleus, phosphoprotein, rna-binding, nuclear protein
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q8WYQ5
• Total number of polymer chains: 1
• Total formula weight: 8888.26

Authors

Senturia, R.,Cascio, D.,Sawaya, M.,Guo, F. (deposition date: 2010-01-14, release date: 2010-07-07, Last modification date: 2024-02-21)

Primary citation

Senturia, R.,Faller, M.,Yin, S.,Loo, J.A.,Cascio, D.,Sawaya, M.R.,Hwang, D.,Clubb, R.T.,Guo, F.
Structure of the dimerization domain of DiGeorge Critical Region 8
Protein Sci., 19:1354-1365, 2010

PubMed Abstract: Maturation of microRNAs (miRNAs, approximately 22nt) from long primary transcripts [primary miRNAs (pri-miRNAs)] is regulated during development and is altered in diseases such as cancer. The first processing step is a cleavage mediated by the Microprocessor complex containing the Drosha nuclease and the RNA-binding protein DiGeorge critical region 8 (DGCR8). We previously reported that dimeric DGCR8 binds heme and that the heme-bound DGCR8 is more active than the heme-free form. Here, we identified a conserved dimerization domain in DGCR8. Our crystal structure of this domain (residues 298-352) at 1.7 A resolution demonstrates a previously unknown use of a WW motif as a platform for extensive dimerization interactions. The dimerization domain of DGCR8 is embedded in an independently folded heme-binding domain and directly contributes to association with heme. Heme-binding-deficient DGCR8 mutants have reduced pri-miRNA processing activity in vitro. Our study provides structural and biochemical bases for understanding how dimerization and heme binding of DGCR8 may contribute to regulation of miRNA biogenesis.

PubMed: 20506313
DOI: 10.1002/pro.414

Experimental method

X-RAY DIFFRACTION (1.701 Å)