Specifying conformational heterogeneity of multi-domain proteins at atomic resolution

Lade...
Vorschaubild
Dateien
Zu diesem Dokument gibt es keine Dateien.
Datum
2023
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
URI (zitierfähiger Link)
ArXiv-ID
Internationale Patentnummer
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Zusammenfassung

The conformational landscape of multi-domain proteins is inherently linked to their specific functions. This also holds for polyubiquitin chains that are assembled by two or more ubiquitin domains connected by a flexible linker thus showing a large interdomain mobility. However, molecular recognition and signal transduction are associated with particular conformational substates that are populated in solution. Here, we apply high-resolution NMR spectroscopy in combination with dual-scale MD simulations to explore the conformational space of K6-, K29-, and K33-linked diubiquitin molecules. The conformational ensembles are evaluated utilizing a paramagnetic cosolute reporting on solvent exposure plus a set of complementary NMR parameters. This approach unravels a conformational heterogeneity of diubiquitins and explains the diversity of structural models that have been determined for K6-, K29-, and K33-linked diubiquitins in free and ligand-bound states so far. We propose a general application of the approach developed here to demystify multi-domain proteins occurring in nature.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
540 Chemie
Schlagwörter
click chemistry, conformational ensembles, conformational heterogeneity, MD simulations, multi-domain proteins, NMR spectroscopy, paramagnetic relaxation enhancement, spin relaxation, protein dynamics, ubiquitin chains
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690SCHNEIDER, Tobias, Kevin SAWADE, Frederic BERNER, Christine PETER, Michael KOVERMANN, 2023. Specifying conformational heterogeneity of multi-domain proteins at atomic resolution. In: Structure. Elsevier. 2023, 31(10), pp. 1259-1274.e10. ISSN 0969-2126. eISSN 1878-4186. Available under: doi: 10.1016/j.str.2023.07.008
BibTex
@article{Schneider2023-10Speci-67597,
  year={2023},
  doi={10.1016/j.str.2023.07.008},
  title={Specifying conformational heterogeneity of multi-domain proteins at atomic resolution},
  number={10},
  volume={31},
  issn={0969-2126},
  journal={Structure},
  pages={1259--1274.e10},
  author={Schneider, Tobias and Sawade, Kevin and Berner, Frederic and Peter, Christine and Kovermann, Michael}
}
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/123456789/67597">
    <dc:contributor>Sawade, Kevin</dc:contributor>
    <dc:language>eng</dc:language>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2023-08-14T07:31:14Z</dcterms:available>
    <dcterms:title>Specifying conformational heterogeneity of multi-domain proteins at atomic resolution</dcterms:title>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2023-08-14T07:31:14Z</dc:date>
    <dc:creator>Kovermann, Michael</dc:creator>
    <dcterms:abstract>The conformational landscape of multi-domain proteins is inherently linked to their specific functions. This also holds for polyubiquitin chains that are assembled by two or more ubiquitin domains connected by a flexible linker thus showing a large interdomain mobility. However, molecular recognition and signal transduction are associated with particular conformational substates that are populated in solution. Here, we apply high-resolution NMR spectroscopy in combination with dual-scale MD simulations to explore the conformational space of K6-, K29-, and K33-linked diubiquitin molecules. The conformational ensembles are evaluated utilizing a paramagnetic cosolute reporting on solvent exposure plus a set of complementary NMR parameters. This approach unravels a conformational heterogeneity of diubiquitins and explains the diversity of structural models that have been determined for K6-, K29-, and K33-linked diubiquitins in free and ligand-bound states so far. We propose a general application of the approach developed here to demystify multi-domain proteins occurring in nature.</dcterms:abstract>
    <dc:contributor>Kovermann, Michael</dc:contributor>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:creator>Peter, Christine</dc:creator>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:creator>Sawade, Kevin</dc:creator>
    <dc:contributor>Berner, Frederic</dc:contributor>
    <dc:contributor>Schneider, Tobias</dc:contributor>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dc:creator>Schneider, Tobias</dc:creator>
    <dc:contributor>Peter, Christine</dc:contributor>
    <dc:creator>Berner, Frederic</dc:creator>
    <dcterms:issued>2023-10</dcterms:issued>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/67597"/>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Ja
Diese Publikation teilen