3KRN

Crystal Structure of C. elegans cell-death-related nuclease 5(CRN-5)

3KRN の概要

• エントリーDOI: 10.2210/pdb3krn/pdb
• 関連するPDBエントリー: 3HKM
• 分子名称: Protein C14A4.5, confirmed by transcript evidence (1 entity in total)
• 機能のキーワード: rnase ph domain, homodimer, exosome, cell-death-related dnase, hydrolase
• 由来する生物種: Caenorhabditis elegans (nematode)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48216.65

構造登録者

Yang, C.-C.,Wang, Y.-T.,Hsiao, Y.-Y.,Doudeva, L.G.,Chow, S.Y.,Yuan, H.S. (登録日: 2009-11-19, 公開日: 2010-01-26, 最終更新日: 2023-11-01)

主引用文献

Yang, C.-C.,Wang, Y.-T.,Hsiao, Y.-Y.,Doudeva, L.G.,Kuo, P.-H.,Chow, S.Y.,Yuan, H.S.
Structural and biochemical characterization of CRN-5 and Rrp46: an exosome component participating in apoptotic DNA degradation
Rna, 16:1748-1759, 2010

PubMed Abstract: Rrp46 was first identified as a protein component of the eukaryotic exosome, a protein complex involved in 3' processing of RNA during RNA turnover and surveillance. The Rrp46 homolog, CRN-5, was subsequently characterized as a cell death-related nuclease, participating in DNA fragmentation during apoptosis in Caenorhabditis elegans. Here we report the crystal structures of CRN-5 and rice Rrp46 (oRrp46) at a resolution of 3.9 A and 2.0 A, respectively. We found that recombinant human Rrp46 (hRrp46), oRrp46, and CRN-5 are homodimers, and that endogenous hRrp46 and oRrp46 also form homodimers in a cellular environment, in addition to their association with a protein complex. Dimeric oRrp46 had both phosphorolytic RNase and hydrolytic DNase activities, whereas hRrp46 and CRN-5 bound to DNA without detectable nuclease activity. Site-directed mutagenesis in oRrp46 abolished either its DNase (E160Q) or RNase (K75E/Q76E) activities, confirming the critical importance of these residues in catalysis or substrate binding. Moreover, CRN-5 directly interacted with the apoptotic nuclease CRN-4 and enhanced the DNase activity of CRN-4, suggesting that CRN-5 cooperates with CRN-4 in apoptotic DNA degradation. Taken together all these results strongly suggest that Rrp46 forms a homodimer separately from exosome complexes and, depending on species, is either a structural or catalytic component of the machinery that cleaves DNA during apoptosis.

PubMed: 20660080
DOI: 10.1261/rna.2180810

実験手法

X-RAY DIFFRACTION (3.918 Å)