The crystal structure of the monomeric reverse transcriptase from Moloney murine leukemia virus
The crystal structure of the monomeric reverse transcriptase from Moloney murine leukemia virus
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DOI：
10.1016/j.str.2004.02.032
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发表时间：
2004-05-01
期刊：
影响因子：
5.7
通讯作者：
Georgiadis, MM
中科院分区：
文献类型：
--
作者：
Das, D;Georgiadis, MM
逆转录酶（RT）是可变结构的多结构域酶，其将RNA和DNA指导的DNA聚合酶活性与RNA：DNA杂合体特异性的RNA酶H活性偶联，以复制逆转录病毒的单链RNA基因组。先前的结构工作已经报道了异二聚体HIV-1和HIV-2 RT。我们现在报告的第一个晶体结构的全长莫洛尼鼠白血病病毒（MMLV）RT在3.0埃分辨率。该结构揭示了一个钳形分子，其由拇指、连接和RNA酶H结构域的相对位置产生，与HIV-1 RT显著不同，并提供了单体逆转录酶的第一个例子。与相关的DNA聚合酶的比较分析表明，一个独特的轨迹的模板引物退出聚合酶活性位点，并提供有关的MMLV RT进行性DNA合成的见解。
Reverse transcriptases (RTs) are multidomain enzymes of variable architecture that couple both RNA- and DNA-directed DNA polymerase activities with an RNase H activity specific for an RNA:DNA hybrid in order to replicate the single-stranded RNA genome of the retrovirus. Previous structural work has been reported for the heterodimeric HIV-1 and HIV-2 RTs. We now report the first crystal structure of the full-length Moloney murine leukemia virus (MMLV) RT at 3.0 Angstrom resolution. The structure reveals a clamp-shaped molecule resulting from the relative positions of the thumb, connection, and RNase H domains that is strikingly different from the HIV-1 RT and provides the first example of a monomeric reverse transcriptase. A comparative analysis with related DNA polymerases suggests a unique trajectory for the template-primer exiting the polymerase active site and provides insights regarding processive DNA synthesis by MMLV RT.