The histone H3-H4 tetramer is a copper reductase enzyme

Narsis Attar; Oscar A. Campos; Maria Vogelauer; Chen Cheng; Yong Xue; Stefan Schmollinger; Lukasz Salwinski; Nathan V. Mallipeddi; Brandon A. Boone; Linda Yen; Sichen Yang; Shannon Zikovich; Jade Dardine; Michael F. Carey; Sabeeha S. Merchant; Siavash K. Kurdistani

doi:10.1126/science.aba8740

The histone H3-H4 tetramer is a copper reductase enzyme

Narsis Attar, Oscar A. Campos, Maria Vogelauer, Chen Cheng, Yong Xue, Stefan Schmollinger, Lukasz Salwinski, Nathan V. Mallipeddi, Brandon A. Boone, Linda Yen, Sichen Yang, Shannon Zikovich, Jade Dardine, Michael F. Carey, Sabeeha S. Merchant, Siavash K. Kurdistani

Research output: Contribution to journal › Article › peer-review

60 Scopus citations

Abstract

Eukaryotic histone H3-H4 tetramers contain a putative copper (Cu2+) binding site at the H3-H3′ dimerization interface with unknown function. The coincident emergence of eukaryotes with global oxygenation, which challenged cellular copper utilization, raised the possibility that histones may function in cellular copper homeostasis. We report that the recombinant Xenopus laevis H3-H4 tetramer is an oxidoreductase enzyme that binds Cu2+ and catalyzes its reduction to Cu1+ in vitro. Loss- A nd gain-of-function mutations of the putative active site residues correspondingly altered copper binding and the enzymatic activity, as well as intracellular Cu1+ abundance and copper-dependent mitochondrial respiration and Sod1 function in the yeast Saccharomyces cerevisiae. The histone H3-H4 tetramer, therefore, has a role other than chromatin compaction or epigenetic regulation and generates biousable Cu1+ ions in eukaryotes.

Original language	English
Pages (from-to)	59-64
Number of pages	6
Journal	Science
Volume	369
Issue number	6499
DOIs	https://doi.org/10.1126/science.aba8740
State	Published - Jul 3 2020
Externally published	Yes

Funding

Funders	Funder number
National Institute of Allergy and Infectious Diseases	P30AI028697
National Institute of Allergy and Infectious Diseases

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title = "The histone H3-H4 tetramer is a copper reductase enzyme",

abstract = "Eukaryotic histone H3-H4 tetramers contain a putative copper (Cu2+) binding site at the H3-H3′ dimerization interface with unknown function. The coincident emergence of eukaryotes with global oxygenation, which challenged cellular copper utilization, raised the possibility that histones may function in cellular copper homeostasis. We report that the recombinant Xenopus laevis H3-H4 tetramer is an oxidoreductase enzyme that binds Cu2+ and catalyzes its reduction to Cu1+ in vitro. Loss- A nd gain-of-function mutations of the putative active site residues correspondingly altered copper binding and the enzymatic activity, as well as intracellular Cu1+ abundance and copper-dependent mitochondrial respiration and Sod1 function in the yeast Saccharomyces cerevisiae. The histone H3-H4 tetramer, therefore, has a role other than chromatin compaction or epigenetic regulation and generates biousable Cu1+ ions in eukaryotes.",

author = "Narsis Attar and Campos, {Oscar A.} and Maria Vogelauer and Chen Cheng and Yong Xue and Stefan Schmollinger and Lukasz Salwinski and Mallipeddi, {Nathan V.} and Boone, {Brandon A.} and Linda Yen and Sichen Yang and Shannon Zikovich and Jade Dardine and Carey, {Michael F.} and Merchant, {Sabeeha S.} and Kurdistani, {Siavash K.}",

year = "2020",

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doi = "10.1126/science.aba8740",

language = "English",

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T1 - The histone H3-H4 tetramer is a copper reductase enzyme

AU - Attar, Narsis

AU - Campos, Oscar A.

AU - Vogelauer, Maria

AU - Cheng, Chen

AU - Xue, Yong

AU - Schmollinger, Stefan

AU - Salwinski, Lukasz

AU - Mallipeddi, Nathan V.

AU - Boone, Brandon A.

AU - Yen, Linda

AU - Yang, Sichen

AU - Zikovich, Shannon

AU - Dardine, Jade

AU - Carey, Michael F.

AU - Merchant, Sabeeha S.

AU - Kurdistani, Siavash K.

PY - 2020/7/3

Y1 - 2020/7/3

N2 - Eukaryotic histone H3-H4 tetramers contain a putative copper (Cu2+) binding site at the H3-H3′ dimerization interface with unknown function. The coincident emergence of eukaryotes with global oxygenation, which challenged cellular copper utilization, raised the possibility that histones may function in cellular copper homeostasis. We report that the recombinant Xenopus laevis H3-H4 tetramer is an oxidoreductase enzyme that binds Cu2+ and catalyzes its reduction to Cu1+ in vitro. Loss- A nd gain-of-function mutations of the putative active site residues correspondingly altered copper binding and the enzymatic activity, as well as intracellular Cu1+ abundance and copper-dependent mitochondrial respiration and Sod1 function in the yeast Saccharomyces cerevisiae. The histone H3-H4 tetramer, therefore, has a role other than chromatin compaction or epigenetic regulation and generates biousable Cu1+ ions in eukaryotes.

AB - Eukaryotic histone H3-H4 tetramers contain a putative copper (Cu2+) binding site at the H3-H3′ dimerization interface with unknown function. The coincident emergence of eukaryotes with global oxygenation, which challenged cellular copper utilization, raised the possibility that histones may function in cellular copper homeostasis. We report that the recombinant Xenopus laevis H3-H4 tetramer is an oxidoreductase enzyme that binds Cu2+ and catalyzes its reduction to Cu1+ in vitro. Loss- A nd gain-of-function mutations of the putative active site residues correspondingly altered copper binding and the enzymatic activity, as well as intracellular Cu1+ abundance and copper-dependent mitochondrial respiration and Sod1 function in the yeast Saccharomyces cerevisiae. The histone H3-H4 tetramer, therefore, has a role other than chromatin compaction or epigenetic regulation and generates biousable Cu1+ ions in eukaryotes.

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DO - 10.1126/science.aba8740

M3 - Article

C2 - 32631887

AN - SCOPUS:85087629567

SN - 0036-8075

VL - 369

SP - 59

EP - 64

JO - Science

JF - Science

IS - 6499

ER -

The histone H3-H4 tetramer is a copper reductase enzyme

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