A Bridge Crosses the Active-Site Canyon of the Epstein-Barr Virus Nuclease with DNase and RNase Activities |
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Authors: | Marlyse Buisson Thibault Géoui David Flot Nicolas Tarbouriech Emmanuel J Wiertz Wim P Burmeister |
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Institution: | 1 Unit of Virus Host Cell Interactions, UMI3265 UJF-EMBL-CNRS, 6 rue Horowitz, F-38000 Grenoble, France 2 Hôpital Michallon, B.P. 217, F-38043 Grenoble Cedex 9, France 3 Department of Medical Microbiology, University Medical Center Utrecht, G04.647, Heidelberglaan 100, NL-3584 CX Utrecht, The Netherlands 4 Institut Universitaire de France, 103 Boulevard St. Michel, F-75005 Paris, France |
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Abstract: | Epstein-Barr virus, a double-stranded DNA (dsDNA) virus, is a major human pathogen from the herpesvirus family. The nuclease is one of the lytic cycle proteins required for successful viral replication. In addition to the previously described endonuclease and exonuclease activities on single-stranded DNA and dsDNA substrates, we observed an RNase activity for Epstein-Barr virus nuclease in the presence of Mn2+, giving a possible explanation for its role in host mRNA degradation. Its crystal structure shows a catalytic core of the D-(D/E)XK nuclease superfamily closely related to the exonuclease from bacteriophage lambda with a bridge across the active-site canyon. This bridge may reduce endonuclease activity, ensure processivity or play a role in strand separation of dsDNA substrates. As the DNA strand that is subject to cleavage is likely to make a sharp turn in front of the bridge, endonuclease activity on single-stranded DNA stretches appears to be possible, explaining the cleavage of circular substrates. |
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Keywords: | dsDNA double-stranded DNA EBV Epstein-Barr virus NPC nasopharyngeal carcinoma ssDNA single-stranded DNA HSV herpes simplex virus NLS nuclear localization signal GFP green fluorescent protein WT WT KSHV Kaposi-sarcoma-related herpesvirus TEV tobacco etch virus ncs non-crystallographic symmetry |
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