Evidence map›Paper›PMID 35051665›Full record

ArticleBiochimica et biophysica acta. Proteins and proteomics2022

Structural mass spectrometry decodes domain interaction and dynamics of the full-length Human Histone Deacetylase 2.

Zoja Soloviev, Joshua M A Bullock, Juliette M B James, Andrea C Sauerwein, Joanne E Nettleship, Raymond J Owens, D Flemming Hansen, Maya Topf, Konstantinos Thalassinos

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochimica et biophysica acta. Proteins and proteomics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 43% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 5 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Zoja SolovievInstitute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6AR, UK. Electronic address: z.nagurnaja.12@alumni.ucl.ac.uk.
Joshua M A BullockInstitute of Structural and Molecular Biology, Birkbeck College, University of London, London WC1E 7HX, UK.
Juliette M B JamesInstitute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6AR, UK.
Andrea C SauerweinInstitute of Structural and Molecular Biology, Birkbeck College, University of London, London WC1E 7HX, UK.
Joanne E NettleshipPPUK, Research Complex at Harwell, Rutherford Appleton Laboratory, Oxford OX11 0FA, UK; Division of Structural Biology, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK.
Raymond J OwensPPUK, Research Complex at Harwell, Rutherford Appleton Laboratory, Oxford OX11 0FA, UK; Division of Structural Biology, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, UK.
D Flemming HansenInstitute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6AR, UK.
Maya TopfInstitute of Structural and Molecular Biology, Birkbeck College, University of London, London WC1E 7HX, UK; Centre for Structural Systems Biology, Heinrich-Pette-Institut, Leibniz-Institut für Experimentelle Virologie, Hamburg, Germany.
Konstantinos ThalassinosInstitute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6AR, UK. Electronic address: k.thalassinos@ucl.ac.uk.
University College London · GBBirkbeck, University of London · GBRutherford Appleton Laboratory · GBInstitute of Structural and Molecular Biology · GB

Funding

Biotechnology and Biological Sciences Research Council BB/H022570/1Biotechnology and Biological Sciences Research Council BB/J014567/1Medical Research Council G0600084Medical Research Council MR/K018779/1Wellcome Trust 104913/Z/14/ZWellcome Trust 209250/Z/17/Z
6 · The paper itself

Abstract

Human Histone Deacetylase 2 (HDAC2) belongs to a conserved enzyme superfamily that regulates deacetylation inside cells. HDAC2 is a drug target as it is known to be upregulated in cancers and neurodegenerative disorders. It consists of globular deacetylase and C-terminus intrinsically-disordered domains [1-3]. To date, there is no full-length structure of HDAC2 available due to the high intrinsic flexibility of its C-terminal domain. The intrinsically-disordered domain, however, is known to be important for the enzymatic function of HDAC2 [1, 4]. Here we combine several structural Mass Spectrometry (MS) methodologies such as denaturing, native, ion mobility and chemical crosslinking, alongside biochemical assays and molecular modelling to study the structure and dynamics of the full-length HDAC2 for the first time. We show that MS can easily dissect heterogeneity inherent within the protein sample and at the same time probe the structural arrangement of the different conformers present. Activity assays combined with data from MS and molecular modelling suggest how the structural dynamics of the C-terminal domain, and its interactions with the catalytic domain, regulate the activity of this enzyme.

Indexed as

Models, MolecularCatalytic DomainCross-Linking ReagentsHistone Deacetylase 2HumansIntrinsically Disordered ProteinsIon Mobility SpectrometryMass SpectrometryMolecular StructureCross-Linking ReagentsHDAC2 protein, humanHistone Deacetylase 2Intrinsically Disordered ProteinsCrosslinkingHuman Histone Deacetylase 2 (HDAC2)Intrinsically-disordered proteinsIon Mobility Mass Spectrometry (IM-MS)Molecular modelling

Identifiers

PMID35051665
PMCPMC8825994
OpenAlexW4206018245

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.