Illuminating structural proteins in viral "dark matter" with metaproteomics
Illuminating structural proteins in viral "dark matter" with metaproteomics
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DOI：
10.1073/pnas.1525139113
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发表时间：
2016-03-01
影响因子：
11.1
通讯作者：
Sullivan, Matthew B.
中科院分区：
文献类型：
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作者：
Brum, Jennifer R.;Ignacio-Espinoza, J. Cesar;Sullivan, Matthew B.
病毒在生态学上具有重要意义，但环境病毒学却受到未注释的基因组序列的限制，这些基因组序列代表了分类和功能上的“病毒暗物质”。“虽然最近的分析进展正在迅速改善分类注释，但识别功能性暗物质仍然存在问题。在这里，我们应用配对元蛋白质组学和dsDNA靶向宏基因组学来识别来自海洋的1，875种病毒体相关蛋白。超过一半的这些蛋白质是新的功能注释，并代表丰富和广泛的病毒宏基因组衍生的蛋白质簇（PC）。一个主要未注释的PC占主导地位的数据集，但结构建模和基因组背景确定这PC作为一个以前未识别的衣壳蛋白从多个未培养的尾病毒家族。此外，在元蛋白质组中五个最丰富的PC中有四个代表了含有HK97样蛋白折叠的衣壳蛋白，这种蛋白折叠以前在许多感染所有三个生命结构域的病毒中发现。这些蛋白质在我们数据集中的主导地位，以及它们在世界海洋中的全球分布，支持了先前的假设，即这种HK97样蛋白质折叠是地球上最丰富的生物结构。总之，这些独立于培养物的分析改进了病毒体相关蛋白质注释，促进了对天然病毒群落内蛋白质的研究，并提供了一种高通量的手段来阐明功能性病毒暗物质。
Viruses are ecologically important, yet environmental virology is limited by dominance of unannotated genomic sequences representing taxonomic and functional "viral dark matter." Although recent analytical advances are rapidly improving taxonomic annotations, identifying functional darkmatter remains problematic. Here, we apply paired metaproteomics and dsDNA-targeted metagenomics to identify 1,875 virion-associated proteins from the ocean. Over one-half of these proteins were newly functionally annotated and represent abundant and widespread viral metagenome-derived protein clusters (PCs). One primarily unannotated PC dominated the dataset, but structural modeling and genomic context identified this PC as a previously unidentified capsid protein from multiple uncultivated tailed virus families. Furthermore, four of the five most abundant PCs in the metaproteome represent capsid proteins containing the HK97-like protein fold previously found in many viruses that infect all three domains of life. The dominance of these proteins within our dataset, as well as their global distribution throughout the world's oceans and seas, supports prior hypotheses that this HK97-like protein fold is the most abundant biological structure on Earth. Together, these culture-independent analyses improve virion-associated protein annotations, facilitate the investigation of proteins within natural viral communities, and offer a high-throughput means of illuminating functional viral dark matter.