Toward understanding the conformational dynamics of RNA ligation.
Toward understanding the conformational dynamics of RNA ligation.
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DOI：
10.1021/bi8018114
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发表时间：
2009-02-03
期刊：
影响因子：
2.9
通讯作者：
McCammont, J. Andrew
中科院分区：
文献类型：
--
作者：
Swift, Robert V.;Durrant, Jacob;Amaro, Rommie E.;McCammont, J. Andrew
锥虫属的成员，包括致病物种布鲁氏锥虫和克氏锥虫，通过称为编辑体的多蛋白复合体编辑其转录后线粒体RNA。在布氏毛滴虫中，RNA在尿苷酸插入和缺失之前被切断。在编辑之后，缺口RNA被两种RNA编辑连接酶(TbREL)中的一种切割。这项研究描述了最近对TbREL1的分子动力学模拟，TbREL1是核苷酸转移酶超家族的一种依赖于ATP的RNA编辑连接酶，是布氏毛虫昆虫和血液形式生存所必需的。本工作根据TbREL1与T4RnL2的同源关系，建立了TbREL1与其全双链RNA(DsRNA)底物的复合体模型。该模拟捕捉了TbREL1在RNA连接前的状态下的动态，为深入了解动质体连接反应的功能动力学和催化机制提供了见解。对于动叶绿体连接酶和更广泛的核苷酸转移酶超家族，揭示了RNA结合和特异性的重要特征。
Members of the genus Trypanosoma, which include the pathogenic species Trypanosoma brucei and Trypanosoma cruzi, edit their post-transcriptional mitochondrial RNA via a multiprotein complex called the editosome. In T. brucei, the RNA is nicked prior to uridylate insertion and deletion. Following editing, nicked RNA is religated by one of two RNA-editing ligases (TbREL). This study describes a recent 70 ns molecular dynamics simulation of TbREL1, an ATP-dependent RNA-editing ligase of the nucleotidyltransferase superfamily that is required for the survival of T. brucei insect and bloodstream forms. In this work, a model of TbREL1 in complex with its full double-stranded RNA (dsRNA) substrate is created on the basis of the homologous relation between TbREL1 and T4 Rnl2. The simulation captures TbREL1 dynamics in the state immediately preceding RNA ligation, providing insights into the functional dynamics and catalytic mechanism of the kinetoplastid ligation reaction. Important features of RNA binding and specificity are revealed for kinetoplastid ligases and the broader nucleotidyltransferase superfamily.
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影响因子：
3.8
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