3hkm
Crystal Structure of rice(Oryza sativa) Rrp46
Structural highlights
FunctionEXOS5_ORYSJ Probable component of the exosome 3'->5' exoribonuclease complex, a complex that degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3'-untranslated regions. May form a homodimer separately from exosome complexes and function in DNA cleavage process. Binds double-stranded DNA (dsDNA) and single-stranded RNA (ssRNA), and possesses hydrolytic DNase and phosphorolytic RNase activities in vitro.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedRrp46 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. Structural and biochemical characterization of CRN-5 and Rrp46: an exosome component participating in apoptotic DNA degradation.,Yang CC, Wang YT, Hsiao YY, Doudeva LG, Kuo PH, Chow SY, Yuan HS RNA. 2010 Sep;16(9):1748-59. Epub 2010 Jul 21. PMID:20660080[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
