Molecular architecture of the Jumonji C family histone demethylase KDM5B

Jerzy Dorosz; Line Hyltoft Kristensen; Nanda G Aduri; Osman Mirza; Rikke Lousen; Saskia Bucciarelli; Ved Mehta; Selene Sellés-Baiget; Sara Marie Øie Solbak; Anders Bach; Pablo Mesa; Pablo Alcon Hernandez; Guillermo Montoya; Tam T. T. N. Nguyen; Kasper D. Rand; Thomas Boesen; Michael Gajhede

doi:10.1038/s41598-019-40573-y

Molecular architecture of the Jumonji C family histone demethylase KDM5B

Jerzy Dorosz, Line Hyltoft Kristensen, Nanda G Aduri, Osman Mirza, Rikke Lousen, Saskia Bucciarelli, Ved Mehta, Selene Sellés-Baiget, Sara Marie Øie Solbak, Anders Bach, Pablo Mesa, Pablo Alcon Hernandez, Guillermo Montoya, Tam T. T. N. Nguyen, Kasper D. Rand, Thomas Boesen, Michael Gajhede

Protein Structure and Function Program

3 Citations (Scopus)

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Abstract

The full length human histone 3 lysine 4 demethylase KDM5B (PLU-1/Jarid1B) has been studied using Hydrogen/Deuterium exchange mass spectrometry, homology modelling, sequence analysis, small angle X-ray scattering and electron microscopy. This first structure on an intact multi-domain Jumonji histone demethylase reveal that the so-called PLU region, in the central region of KDM5B, has a curved α-helical three-dimensional structure, that acts as a rigid linker between the catalytic core and a region comprising four α-helices, a loop comprising the PHD2 domain, two large intrinsically disordered loops and the PHD3 domain in close proximity. The dumbbell shaped and curved KDM5B architecture observed by electron microscopy is complementary to the nucleosome surface and has a striking overall similarity to that of the functionally related KDM1A/CoREST complex. This could suggest that there are similarities between the demethylation mechanisms employed by the two histone 3 lysine 4 demethylases at the molecular level.

Original language	English
Article number	4019
Journal	Scientific Reports
Volume	9
Number of pages	13
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-019-40573-y
Publication status	Published - 1 Dec 2019

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Dorosz, J., Kristensen, L. H., Aduri, N. G., Mirza, O., Lousen, R., Bucciarelli, S., Mehta, V., Sellés-Baiget, S., Solbak, S. M. Ø., Bach, A., Mesa, P., Hernandez, P. A., Montoya, G., Nguyen, T. T. T. N., Rand, K. D., Boesen, T., & Gajhede, M. (2019). Molecular architecture of the Jumonji C family histone demethylase KDM5B. Scientific Reports, 9, [4019]. https://doi.org/10.1038/s41598-019-40573-y

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title = "Molecular architecture of the Jumonji C family histone demethylase KDM5B",

abstract = "The full length human histone 3 lysine 4 demethylase KDM5B (PLU-1/Jarid1B) has been studied using Hydrogen/Deuterium exchange mass spectrometry, homology modelling, sequence analysis, small angle X-ray scattering and electron microscopy. This first structure on an intact multi-domain Jumonji histone demethylase reveal that the so-called PLU region, in the central region of KDM5B, has a curved α-helical three-dimensional structure, that acts as a rigid linker between the catalytic core and a region comprising four α-helices, a loop comprising the PHD2 domain, two large intrinsically disordered loops and the PHD3 domain in close proximity. The dumbbell shaped and curved KDM5B architecture observed by electron microscopy is complementary to the nucleosome surface and has a striking overall similarity to that of the functionally related KDM1A/CoREST complex. This could suggest that there are similarities between the demethylation mechanisms employed by the two histone 3 lysine 4 demethylases at the molecular level.",

author = "Jerzy Dorosz and Kristensen, {Line Hyltoft} and Aduri, {Nanda G} and Osman Mirza and Rikke Lousen and Saskia Bucciarelli and Ved Mehta and Selene Sell{\'e}s-Baiget and Solbak, {Sara Marie {\O}ie} and Anders Bach and Pablo Mesa and Hernandez, {Pablo Alcon} and Guillermo Montoya and Nguyen, {Tam T. T. N.} and Rand, {Kasper D.} and Thomas Boesen and Michael Gajhede",

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doi = "10.1038/s41598-019-40573-y",

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AU - Dorosz, Jerzy

AU - Kristensen, Line Hyltoft

AU - Aduri, Nanda G

AU - Mirza, Osman

AU - Lousen, Rikke

AU - Bucciarelli, Saskia

AU - Mehta, Ved

AU - Sellés-Baiget, Selene

AU - Solbak, Sara Marie Øie

AU - Bach, Anders

AU - Mesa, Pablo

AU - Hernandez, Pablo Alcon

AU - Montoya, Guillermo

AU - Nguyen, Tam T. T. N.

AU - Rand, Kasper D.

AU - Boesen, Thomas

AU - Gajhede, Michael

PY - 2019/12/1

Y1 - 2019/12/1

N2 - The full length human histone 3 lysine 4 demethylase KDM5B (PLU-1/Jarid1B) has been studied using Hydrogen/Deuterium exchange mass spectrometry, homology modelling, sequence analysis, small angle X-ray scattering and electron microscopy. This first structure on an intact multi-domain Jumonji histone demethylase reveal that the so-called PLU region, in the central region of KDM5B, has a curved α-helical three-dimensional structure, that acts as a rigid linker between the catalytic core and a region comprising four α-helices, a loop comprising the PHD2 domain, two large intrinsically disordered loops and the PHD3 domain in close proximity. The dumbbell shaped and curved KDM5B architecture observed by electron microscopy is complementary to the nucleosome surface and has a striking overall similarity to that of the functionally related KDM1A/CoREST complex. This could suggest that there are similarities between the demethylation mechanisms employed by the two histone 3 lysine 4 demethylases at the molecular level.

AB - The full length human histone 3 lysine 4 demethylase KDM5B (PLU-1/Jarid1B) has been studied using Hydrogen/Deuterium exchange mass spectrometry, homology modelling, sequence analysis, small angle X-ray scattering and electron microscopy. This first structure on an intact multi-domain Jumonji histone demethylase reveal that the so-called PLU region, in the central region of KDM5B, has a curved α-helical three-dimensional structure, that acts as a rigid linker between the catalytic core and a region comprising four α-helices, a loop comprising the PHD2 domain, two large intrinsically disordered loops and the PHD3 domain in close proximity. The dumbbell shaped and curved KDM5B architecture observed by electron microscopy is complementary to the nucleosome surface and has a striking overall similarity to that of the functionally related KDM1A/CoREST complex. This could suggest that there are similarities between the demethylation mechanisms employed by the two histone 3 lysine 4 demethylases at the molecular level.

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DO - 10.1038/s41598-019-40573-y

M3 - Journal article

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SN - 2045-2322

VL - 9

JO - Scientific Reports

JF - Scientific Reports

M1 - 4019

ER -

Molecular architecture of the Jumonji C family histone demethylase KDM5B

Abstract

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