Towards a molecular basis of ubiquitin signaling : a dual-scale simulation study of ubiquitin dimers

Berg, Andrej; Kukharenko, Oleksandra; Scheffner, Martin; Peter, Christine

Towards a molecular basis of ubiquitin signaling : a dual-scale simulation study of ubiquitin dimers

Dateien

Berg_2-12szprdn1k4p75.pdfGröße: 1.96 MBDownloads: 335

Datum

2018

Open Access-Veröffentlichung

Open Access Gold

Sammlungen

Chemie
Biologie
Zukunftskolleg

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

PLoS computational biology. 2018, 14(11), e1006589. eISSN 1553-7358. Available under: doi: 10.1371/journal.pcbi.1006589

Zusammenfassung

Covalent modification of proteins by ubiquitin or ubiquitin chains is one of the most prevalent post-translational modifications in eukaryotes. Different types of ubiquitin chains are assumed to selectively signal respectively modified proteins for different fates. In support of this hypothesis, structural studies have shown that the eight possible ubiquitin dimers adopt different conformations. However, at least in some cases, these structures cannot sufficiently explain the molecular basis of the selective signaling mechanisms. This indicates that the available structures represent only a few distinct conformations within the entire conformational space adopted by a ubiquitin dimer. Here, molecular simulations on different levels of resolution can complement the structural information. We have combined exhaustive coarse grained and atomistic simulations of all eight possible ubiquitin dimers with a suitable dimensionality reduction technique and a new method to characterize protein-protein interfaces and the conformational landscape of protein conjugates. We found that ubiquitin dimers exhibit characteristic linkage type-dependent properties in solution, such as interface stability and the character of contacts between the subunits, which can be directly correlated with experimentally observed linkage-specific properties.

Author summary
Post-translational modification of proteins by covalent attachment of ubiquitin is a key cellular process, regulating for example the fate and recycling of proteins. We present a new method to combine multiscale simulation with advanced analysis methods to characterize the states of ubiquitin-ubiquitin conjugates. We found that the linkage position affects the conformational space of ubiquitin dimers, determining the number and stability of relevant states, the character of subunit contacts and the nature of the surface exposed to possible binding partners.

Fachgebiet (DDC)

540 Chemie

Zitieren

ISO 690

BERG, Andrej, Oleksandra KUKHARENKO, Martin SCHEFFNER, Christine PETER, 2018. Towards a molecular basis of ubiquitin signaling : a dual-scale simulation study of ubiquitin dimers. In: PLoS computational biology. 2018, 14(11), e1006589. eISSN 1553-7358. Available under: doi: 10.1371/journal.pcbi.1006589

BibTex

@article{Berg2018-11Towar-44400,
  year={2018},
  doi={10.1371/journal.pcbi.1006589},
  title={Towards a molecular basis of ubiquitin signaling : a dual-scale simulation study of ubiquitin dimers},
  number={11},
  volume={14},
  journal={PLoS computational biology},
  author={Berg, Andrej and Kukharenko, Oleksandra and Scheffner, Martin and Peter, Christine},
  note={Article Number: e1006589}
}

RDF

<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/44400">
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/44400/3/Berg_2-12szprdn1k4p75.pdf"/>
    <dc:contributor>Berg, Andrej</dc:contributor>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/52"/>
    <dc:creator>Kukharenko, Oleksandra</dc:creator>
    <dc:creator>Scheffner, Martin</dc:creator>
    <dc:creator>Berg, Andrej</dc:creator>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/44400/3/Berg_2-12szprdn1k4p75.pdf"/>
    <dc:creator>Peter, Christine</dc:creator>
    <dc:contributor>Kukharenko, Oleksandra</dc:contributor>
    <dc:contributor>Scheffner, Martin</dc:contributor>
    <dcterms:issued>2018-11</dcterms:issued>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/44400"/>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2018-12-21T10:35:26Z</dcterms:available>
    <dc:contributor>Peter, Christine</dc:contributor>
    <dc:language>eng</dc:language>
    <dcterms:title>Towards a molecular basis of ubiquitin signaling : a dual-scale simulation study of ubiquitin dimers</dcterms:title>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2018-12-21T10:35:26Z</dc:date>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dcterms:abstract xml:lang="eng">Covalent modification of proteins by ubiquitin or ubiquitin chains is one of the most prevalent post-translational modifications in eukaryotes. Different types of ubiquitin chains are assumed to selectively signal respectively modified proteins for different fates. In support of this hypothesis, structural studies have shown that the eight possible ubiquitin dimers adopt different conformations. However, at least in some cases, these structures cannot sufficiently explain the molecular basis of the selective signaling mechanisms. This indicates that the available structures represent only a few distinct conformations within the entire conformational space adopted by a ubiquitin dimer. Here, molecular simulations on different levels of resolution can complement the structural information. We have combined exhaustive coarse grained and atomistic simulations of all eight possible ubiquitin dimers with a suitable dimensionality reduction technique and a new method to characterize protein-protein interfaces and the conformational landscape of protein conjugates. We found that ubiquitin dimers exhibit characteristic linkage type-dependent properties in solution, such as interface stability and the character of contacts between the subunits, which can be directly correlated with experimentally observed linkage-specific properties.&lt;br /&gt;&lt;br /&gt;Author summary&lt;br /&gt;Post-translational modification of proteins by covalent attachment of ubiquitin is a key cellular process, regulating for example the fate and recycling of proteins. We present a new method to combine multiscale simulation with advanced analysis methods to characterize the states of ubiquitin-ubiquitin conjugates. We found that the linkage position affects the conformational space of ubiquitin dimers, determining the number and stability of relevant states, the character of subunit contacts and the nature of the surface exposed to possible binding partners.</dcterms:abstract>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dc:rights>Attribution 4.0 International</dc:rights>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/52"/>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/>
  </rdf:Description>
</rdf:RDF>

Universitätsbibliographie

Ja

Begutachtet

Ja