Melbournevirus encodes a shorter H2B-H2A doublet histone variant that forms structurally distinct nucleosome structures

Abstract 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 ami...

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Main Authors: Alejandro Villalta, Hugo Bisio, Chelsea M. Toner, Chantal Abergel, Karolin Luger
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-62031-2
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author Alejandro Villalta
Hugo Bisio
Chelsea M. Toner
Chantal Abergel
Karolin Luger
author_facet Alejandro Villalta
Hugo Bisio
Chelsea M. Toner
Chantal Abergel
Karolin Luger
author_sort Alejandro Villalta
collection DOAJ
description Abstract 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.
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spelling doaj-art-5cf48656a14845aa984f3655cbe2c4312025-08-20T03:05:14ZengNature PortfolioNature Communications2041-17232025-07-0116111010.1038/s41467-025-62031-2Melbournevirus encodes a shorter H2B-H2A doublet histone variant that forms structurally distinct nucleosome structuresAlejandro Villalta0Hugo Bisio1Chelsea M. Toner2Chantal Abergel3Karolin Luger4Department of Biochemistry, University of Colorado BoulderAix–Marseille University, Centre National de la Recherche Scientifique, Information Génomique & Structurale, Unité Mixte de Recherche 7256 (Institut de Microbiologie de la Méditerranée, FR3479, IM2B)Department of Biochemistry, University of Colorado BoulderAix–Marseille University, Centre National de la Recherche Scientifique, Information Génomique & Structurale, Unité Mixte de Recherche 7256 (Institut de Microbiologie de la Méditerranée, FR3479, IM2B)Department of Biochemistry, University of Colorado BoulderAbstract 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.https://doi.org/10.1038/s41467-025-62031-2
spellingShingle Alejandro Villalta
Hugo Bisio
Chelsea M. Toner
Chantal Abergel
Karolin Luger
Melbournevirus encodes a shorter H2B-H2A doublet histone variant that forms structurally distinct nucleosome structures
Nature Communications
title Melbournevirus encodes a shorter H2B-H2A doublet histone variant that forms structurally distinct nucleosome structures
title_full Melbournevirus encodes a shorter H2B-H2A doublet histone variant that forms structurally distinct nucleosome structures
title_fullStr Melbournevirus encodes a shorter H2B-H2A doublet histone variant that forms structurally distinct nucleosome structures
title_full_unstemmed Melbournevirus encodes a shorter H2B-H2A doublet histone variant that forms structurally distinct nucleosome structures
title_short Melbournevirus encodes a shorter H2B-H2A doublet histone variant that forms structurally distinct nucleosome structures
title_sort melbournevirus encodes a shorter h2b h2a doublet histone variant that forms structurally distinct nucleosome structures
url https://doi.org/10.1038/s41467-025-62031-2
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