Iyer Lakshminarayan M, Koonin Eugene V, Aravind L
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Genome Biol. 2002;3(3):RESEARCH0012. doi: 10.1186/gb-2002-3-3-research0012. Epub 2002 Feb 13.
Viral DNA-binding proteins have served as good models to study the biochemistry of transcription regulation and chromatin dynamics. Computational analysis of viral DNA-binding regulatory proteins and identification of their previously undetected homologs encoded by cellular genomes might lead to a better understanding of their function and evolution in both viral and cellular systems.
The phyletic range and the conserved DNA-binding domains of the viral regulatory proteins of the poxvirus D6R/N1R and baculoviral Bro protein families have not been previously defined. Using computational analysis, we show that the amino-terminal module of the D6R/N1R proteins defines a novel, conserved DNA-binding domain (the KilA-N domain) that is found in a wide range of proteins of large bacterial and eukaryotic DNA viruses. The KilA-N domain is suggested to be homologous to the fungal DNA-binding APSES domain. We provide evidence for the KilA-N and APSES domains sharing a common fold with the nucleic acid-binding modules of the LAGLIDADG nucleases and the amino-terminal domains of the tRNA endonuclease. The amino-terminal module of the Bro proteins is another, distinct DNA-binding domain (the Bro-N domain) that is present in proteins whose domain architectures parallel those of the KilA-N domain-containing proteins. A detailed analysis of the KilA-N and Bro-N domains and the associated domains points to extensive domain shuffling and lineage-specific gene family expansion within DNA virus genomes.
We define a large class of novel viral DNA-binding proteins and their cellular homologs and identify their domain architectures. On the basis of phyletic pattern analysis we present evidence for a probable viral origin of the fungus-specific cell-cycle regulatory transcription factors containing the APSES DNA-binding domain. We also demonstrate the extensive role of lineage-specific gene expansion and domain shuffling, within a limited set of approximately 24 domains, in the generation of the diversity of virus-specific regulatory proteins.
病毒DNA结合蛋白一直是研究转录调控生物化学和染色质动力学的良好模型。对病毒DNA结合调节蛋白进行计算分析，并鉴定细胞基因组编码的先前未检测到的同源物，可能有助于更好地理解它们在病毒和细胞系统中的功能与进化。
痘病毒D6R/N1R和杆状病毒Bro蛋白家族的病毒调节蛋白的系统发育范围和保守DNA结合结构域此前尚未明确。通过计算分析，我们发现D6R/N1R蛋白的氨基末端模块定义了一个新的保守DNA结合结构域（KilA-N结构域），该结构域存在于多种大型细菌和真核DNA病毒的蛋白质中。KilA-N结构域被认为与真菌DNA结合APSES结构域同源。我们提供证据表明，KilA-N和APSES结构域与LAGLIDADG核酸酶的核酸结合模块以及tRNA内切核酸酶的氨基末端结构域具有共同的折叠方式。Bro蛋白的氨基末端模块是另一种不同的DNA结合结构域（Bro-N结构域），存在于结构域结构与含KilA-N结构域的蛋白质平行的蛋白质中。对KilA-N和Bro-N结构域以及相关结构域的详细分析表明，DNA病毒基因组中存在广泛的结构域重排和谱系特异性基因家族扩张。
我们定义了一大类新型病毒DNA结合蛋白及其细胞同源物，并确定了它们的结构域结构。基于系统发育模式分析，我们提供证据表明，含有APSES DNA结合结构域的真菌特异性细胞周期调节转录因子可能起源于病毒。我们还证明了在大约24个有限的结构域中，谱系特异性基因扩张和结构域重排在产生病毒特异性调节蛋白多样性方面发挥了广泛作用。
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