Villalta Alejandro, Bisio Hugo, Toner Chelsea M, Abergel Chantal, Luger Karolin
Department of Biochemistry, University of Colorado Boulder, Boulder, CO, USA.
Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, CO, USA.
Nat Commun. 2025 Jul 26;16(1):6903. doi: 10.1038/s41467-025-62031-2.
Unique among viruses, some giant viruses utilize histones to organize their genomes into nucleosomes. Melbournevirus encodes a distinct H2B-H2A histone doublet variant in addition to the canonical H4-H3 and H2B-H2A doublets. This viral histone variant has a truncated H2B portion and its amino acid sequence deviates from that of the main viral H2B-H2A throughout the entire coding region. It is less abundant than the main H2B-H2A doublet, is likely essential for melbournevirus fitness, and is conserved in all Marseilleviridae. The cryo-EM structure of a nucleosome-like particle reconstituted with this H2B-H2A variant and viral H4-H3 reveals that only 90 base pairs of DNA are stably bound, significantly less than in eukaryotic nucleosomes and viral nucleosomes made with the main fused viral histone doublets. The reduced ability to bind DNA can be attributed to structural differences between variant and main H2B-H2A. Variant melbournevirus nucleosomes are less stable, possibly aiding rapid genome unpacking to initiate gene expression. Our results highlight the remarkable propensity of giant viruses to appropriate the utility of histones for their specialized purposes.
在病毒中独一无二的是，一些巨型病毒利用组蛋白将其基因组组织成核小体。墨尔本病毒除了编码典型的H4-H3和H2B-H2A双联体之外，还编码一种独特的H2B-H2A组蛋白双联体变体。这种病毒组蛋白变体的H2B部分被截短，并且其氨基酸序列在整个编码区域都与主要的病毒H2B-H2A不同。它比主要的H2B-H2A双联体丰度低，可能对墨尔本病毒的适应性至关重要，并且在所有马赛病毒科中都保守。用这种H2B-H2A变体和病毒H4-H3重构的类核小体颗粒的冷冻电镜结构显示，只有90个碱基对的DNA能稳定结合，这明显少于用主要的融合病毒组蛋白双联体形成的真核核小体和病毒核小体。结合DNA能力的降低可归因于变体和主要H2B-H2A之间的结构差异。变体墨尔本病毒核小体稳定性较低，这可能有助于快速解开基因组以启动基因表达。我们的结果突出了巨型病毒为其特殊目的而挪用组蛋白用途的显著倾向。
