Iyer Lakshminarayan M, Makarova Kira S, Koonin Eugene V, Aravind L
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Nucleic Acids Res. 2004 Oct 5;32(17):5260-79. doi: 10.1093/nar/gkh828. Print 2004.
Recently, it has been shown that a predicted P-loop ATPase (the HerA or MlaA protein), which is highly conserved in archaea and also present in many bacteria but absent in eukaryotes, has a bidirectional helicase activity and forms hexameric rings similar to those described for the TrwB ATPase. In this study, the FtsK-HerA superfamily of P-loop ATPases, in which the HerA clade comprises one of the major branches, is analyzed in detail. We show that, in addition to the FtsK and HerA clades, this superfamily includes several families of characterized or predicted ATPases which are predominantly involved in extrusion of DNA and peptides through membrane pores. The DNA-packaging ATPases of various bacteriophages and eukaryotic double-stranded DNA viruses also belong to the FtsK-HerA superfamily. The FtsK protein is the essential bacterial ATPase that is responsible for the correct segregation of daughter chromosomes during cell division. The structural and evolutionary relationship between HerA and FtsK and the nearly perfect complementarity of their phyletic distributions suggest that HerA similarly mediates DNA pumping into the progeny cells during archaeal cell division. It appears likely that the HerA and FtsK families diverged concomitantly with the archaeal-bacterial division and that the last universal common ancestor of modern life forms had an ancestral DNA-pumping ATPase that gave rise to these families. Furthermore, the relationship of these cellular proteins with the packaging ATPases of diverse DNA viruses suggests that a common DNA pumping mechanism might be operational in both cellular and viral genome segregation. The herA gene forms a highly conserved operon with the gene for the NurA nuclease and, in many archaea, also with the orthologs of eukaryotic double-strand break repair proteins MRE11 and Rad50. HerA is predicted to function in a complex with these proteins in DNA pumping and repair of double-stranded breaks introduced during this process and, possibly, also during DNA replication. Extensive comparative analysis of the 'genomic context' combined with in-depth sequence analysis led to the prediction of numerous previously unnoticed nucleases of the NurA superfamily, including a specific version that is likely to be the endonuclease component of a novel restriction-modification system. This analysis also led to the identification of previously uncharacterized nucleases, such as a novel predicted nuclease of the Sir2-type Rossmann fold, and phosphatases of the HAD superfamily that are likely to function as partners of the FtsK-HerA superfamily ATPases.
最近的研究表明，一种预测的P环ATP酶（HerA或MlaA蛋白）在古菌中高度保守，在许多细菌中也有存在，但在真核生物中不存在，它具有双向解旋酶活性，并形成类似于TrwB ATP酶的六聚体环。在本研究中，对P环ATP酶的FtsK - HerA超家族进行了详细分析，其中HerA进化枝是主要分支之一。我们发现，除了FtsK和HerA进化枝外，这个超家族还包括几个已鉴定或预测的ATP酶家族，它们主要参与DNA和肽通过膜孔的挤出。各种噬菌体和真核双链DNA病毒的DNA包装ATP酶也属于FtsK - HerA超家族。FtsK蛋白是细菌中必需的ATP酶，负责细胞分裂过程中子代染色体的正确分离。HerA和FtsK之间的结构和进化关系以及它们系统发育分布的近乎完美的互补性表明，HerA在古菌细胞分裂过程中同样介导DNA泵入子代细胞。HerA和FtsK家族似乎与古菌 - 细菌的分化同时发生分歧，现代生命形式的最后一个普遍共同祖先拥有一种祖先DNA泵ATP酶，产生了这些家族。此外，这些细胞蛋白与各种DNA病毒的包装ATP酶之间的关系表明，一种共同的DNA泵机制可能在细胞和病毒基因组分离中起作用。herA基因与NurA核酸酶基因形成一个高度保守的操纵子，在许多古菌中，还与真核双链断裂修复蛋白MRE11和Rad50的直系同源基因形成操纵子。预计HerA与这些蛋白质在DNA泵入以及在此过程中引入的双链断裂的修复中形成复合物发挥作用，并且可能在DNA复制过程中也发挥作用。对“基因组环境”进行广泛的比较分析并结合深入的序列分析，预测了许多以前未被注意到的NurA超家族核酸酶，包括一个可能是新型限制 - 修饰系统内切核酸酶成分的特定版本。该分析还导致鉴定出以前未表征的核酸酶，例如一种新型预测的Sir2型罗斯曼折叠核酸酶，以及可能作为FtsK - HerA超家族ATP酶伙伴发挥作用的HAD超家族磷酸酶。
