A Bridge Crosses the Active-Site Canyon of the Epstein-Barr Virus Nuclease with DNase and RNase Activities
A Bridge Crosses the Active-Site Canyon of the Epstein-Barr Virus Nuclease with DNase and RNase Activities
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DOI：
10.1016/j.jmb.2009.06.034
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发表时间：
2009-08-28
影响因子：
5.6
通讯作者：
Burmeister, Wim P.
中科院分区：
文献类型：
--
作者：
Buisson, Marlyse;Geoui, Thibault;Burmeister, Wim P.
爱泼斯坦-巴尔病毒是一种双链DNA（dsDNA）病毒，是疱疹病毒家族的主要人类病原体。核酸酶是成功病毒复制所需的裂解周期蛋白之一。除了先前描述的核酸内切酶和核酸外切酶对单链DNA和双链DNA底物的活性之外，我们观察到在Mn 2+存在下Epstein-Barr病毒核酸酶的RNA酶活性，从而对其在宿主mRNA降解中的作用给出了可能的解释。其晶体结构显示D-（D/E）XK核酸酶超家族的催化核心，其与来自λ噬菌体的核酸外切酶密切相关，具有跨越活性位点峡谷的桥。该桥可以降低核酸内切酶活性，确保持续合成能力或在dsDNA底物的链分离中发挥作用。由于受到切割的DNA链很可能在桥的前面急转弯，单链DNA片段上的核酸内切酶活性似乎是可能的，解释了环状底物的切割。(C)2009爱思唯尔有限公司保留所有权利。
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. (C) 2009 Elsevier Ltd. All rights reserved.