NrS-1 is the first known phage that can infect Epsilonproteobacteria, one of the predominant primary producers in the deep-sea hydrothermal vent ecosystems. NrS-1 polymerase is a multidomain enzyme and is one key component of the phage replisome. The N-terminal Prim/Pol and HBD domains are responsible for DNA polymerization and de novo primer synthesis activities of NrS-1 polymerase. However, the structure and function of the C-terminus (CTR) of NrS-1 polymerase are poorly understood. Here, we report two crystal structures, showing that NrS-1 CTR adopts one unique hexameric ring-shaped conformation. Although the central helicase domain of NrS-1 CTR shares structural similarity with the superfamily III helicases, the folds of the Head and Tail domains are completely novel. Via mutagenesis and in vitro biochemical analysis, we identified many residues important for the helicase and polymerization activities of NrS-1 polymerase. In addition to NrS-1 polymerase, our study may also help us identify and understand the functions of multidomain polymerases expressed by many NrS-1 related phages.

中文翻译：

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结构研究揭示了深海通风噬菌体NrS-1聚合酶的环状结构。

NrS-1是第一个已知的能够感染Epsilon变形细菌的噬菌体，Epsilon变形细菌是深海热液喷口生态系统中主要的初级生产者之一。NrS-1聚合酶是一种多域酶，是噬菌体复制体的关键组成部分。N末端的Prim / Pol和HBD结构域负责DNA聚合和NrS-1聚合酶的从头引物合成活性。但是，人们对NrS-1聚合酶C末端（CTR）的结构和功能了解甚少。在这里，我们报告了两个晶体结构，表明NrS-1 CTR采用一种独特的六聚体环状构象。尽管NrS-1 CTR的中央解旋酶结构域与超家族III解旋酶具有结构相似性，但Head和Tail域的折叠是完全新颖的。通过诱变和体外生化分析，我们鉴定了许多对NrS-1聚合酶的解旋酶和聚合活性重要的残基。除了NrS-1聚合酶，我们的研究还可以帮助我们识别和了解许多NrS-1相关噬菌体表达的多域聚合酶的功能。