Structure of the RNA-dependent RNA polymerase of poliovirus
Structure of the RNA-dependent RNA polymerase of poliovirus
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DOI：
10.1016/s0969-2126(97)00261-x
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发表时间：
1997-08-15
期刊：
影响因子：
5.7
通讯作者：
Schultz, SC
中科院分区：
文献类型：
--
作者：
Hansen, JL;Long, AM;Schultz, SC
背景：RNA病毒复制的核心是依赖于RNA的RNA聚合酶。53 kDa脊髓灰质炎病毒聚合酶与其他病毒和可能的宿主蛋白一起在宿主细胞质中进行病毒RNA复制。RNA依赖性RNA聚合酶包括与逆转录酶具有有限序列相似性的不同类别的聚合酶先前报道的RNA依赖性DNA聚合酶、DNA依赖性DNA聚合酶和DNA依赖性RNA聚合酶的结构表明，不同聚合酶类别之间存在结构和进化关系。我们已经通过X射线晶体学在2.6埃分辨率下确定了脊髓灰质炎病毒RNA依赖性RNA聚合酶的结构。它具有与其他聚合酶相同的整体形状，通常通过类比描述为右手。脊髓灰质炎病毒聚合酶的“手指”和“拇指”亚结构域的结构不同于其他聚合酶的结构域，但棕榈亚结构域包含与其他聚合酶非常相似的核心结构。这种保守的核心结构由四个描述为RNA依赖性聚合酶的氨基酸序列基序组成。这些基序的基于结构的比对使我们能够修改和扩展以前的序列和结构比对，以便将序列保守性与功能联系起来。广泛的区域中观察到的晶体中的聚合酶-聚合酶的相互作用表明一个不寻常的高阶结构，我们认为是重要的聚合酶function.Conclusions：作为第一个例子的RNA依赖的RNA聚合酶的结构，脊髓灰质炎病毒聚合酶的结构提供了一个更好的理解聚合酶的结构，功能和进化。此外，它还深入了解了一种不寻常的高级结构，这种结构可能对脊髓灰质炎病毒聚合酶功能至关重要。
Background: The central player in the replication of RNA Viruses is the viral RNA-dependent RNA polymerase. The 53 kDa poliovirus polymerase, together with other viral and possibly host proteins, carries out viral RNA replication in the host cell cytoplasm. RNA-dependent RNA polymerases comprise a distinct category of polymerases that have limited sequence similarity to reverse transcriptases (RNA-dependent DNA polymerases) and perhaps also to DNA-dependent polymerases, Previously reported structures of RNA-dependent DNA polymerases, DNA-dependent DNA polymerases and a DNA-dependent RNA polymerase show that structural and evolutionary relationships exist between the different polymerase categories.Results: We have determined the structure of the RNA-dependent RNA polymerase of poliovirus at 2.6 Angstrom resolution by X-ray crystallography. It has the same overall shape as other polymerases, commonly described by analogy to a right hand. The structures of the 'fingers' and 'thumb' subdomains of poliovirus polymerase differ from those of other polymerases, but the palm subdomain contains a core structure very similar to that of other polymerases. This conserved core structure is composed of four of the amino acid sequence motifs described for RNA-dependent polymerases. Structure-based alignments of these motifs has enabled us to modify and extend previous sequence and structural alignments so as to relate sequence conservation to function. Extensive regions of polymerase-polymerase interactions observed in the crystals suggest an unusual higher order structure that we believe is important for polymerase function.Conclusions: As a first example of a structure of an RNA-dependent RNA polymerase, the poliovirus polymerase structure provides for a better understanding of polymerase structure, function and evolution. In addition, it has yielded insights into an unusual higher order structure that may be critical for poliovirus polymerase function.