| Autor: |
Michael R. Sawaya, Feng Guo, Duilio Cascio, Michael Faller, Joseph A. Loo, Rachel Senturia, Sheng Yin, Daniel Hwang, Robert T. Clubb |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
Protein Science. 19:1354-1365 |
| ISSN: |
0961-8368 |
| DOI: |
10.1002/pro.414 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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