Publikation:

Observation of Oligomeric States Indicates a High Structural Flexibility Required for the Onset of Polyglutamine Fibrillization

Lade...
Vorschaubild

Dateien

Zu diesem Dokument gibt es keine Dateien.

Datum

2022

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
Core Facility der Universität Konstanz

Gesperrt bis

Titel in einer weiteren Sprache

Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published

Erschienen in

The Journal of Physical Chemistry Letters. American Chemical Society (ACS). 2022, 13(20), pp. 4543-4548. eISSN 1948-7185. Available under: doi: 10.1021/acs.jpclett.2c00203

Zusammenfassung

Polyglutamine (polyQ) diseases are caused by misfolding and aggregation of expanded polyQ tracts in the affected protein. PolyQ fibrils have been studied in detail; however, less is known about oligomeric precursor states. By a combination of time-resolved temperature-jump (T-jump) infrared (IR) spectroscopy and an appropriately tailored polyQ model peptide, we succeeded in disentangling conformational dynamics in the heterogeneous ensemble of states evolving during aggregation. Individual structural elements could be differentiated by IR-specific signatures, i.e., hairpin monomers, β-structured oligomers, and disordered structure. Submillisecond dynamics were observed for early oligomeric states in contrast to the slow dynamics of fibril growth. We propose that a high structural flexibility of oligomers is required to initiate fibril formation, but not after a fibrillar structure has consolidated and the fibril just grows. Our study reveals that structural flexibility changes at different stages in the aggregation process, from fibril initiation to fibril growth.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
540 Chemie

Schlagwörter

Konferenz

Rezension
undefined / . - undefined, undefined

Forschungsvorhaben

Organisationseinheiten

Zeitschriftenheft

Zugehörige Datensätze in KOPS

Zitieren

ISO 690SIU, Ho-Wah, Karin HAUSER, 2022. Observation of Oligomeric States Indicates a High Structural Flexibility Required for the Onset of Polyglutamine Fibrillization. In: The Journal of Physical Chemistry Letters. American Chemical Society (ACS). 2022, 13(20), pp. 4543-4548. eISSN 1948-7185. Available under: doi: 10.1021/acs.jpclett.2c00203
BibTex
@article{Siu2022-05-26Obser-57831,
  year={2022},
  doi={10.1021/acs.jpclett.2c00203},
  title={Observation of Oligomeric States Indicates a High Structural Flexibility Required for the Onset of Polyglutamine Fibrillization},
  number={20},
  volume={13},
  journal={The Journal of Physical Chemistry Letters},
  pages={4543--4548},
  author={Siu, Ho-Wah and Hauser, Karin}
}
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/123456789/57831">
    <dc:creator>Hauser, Karin</dc:creator>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-06-23T13:22:26Z</dcterms:available>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/57831"/>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:contributor>Siu, Ho-Wah</dc:contributor>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dc:contributor>Hauser, Karin</dc:contributor>
    <dcterms:abstract xml:lang="eng">Polyglutamine (polyQ) diseases are caused by misfolding and aggregation of expanded polyQ tracts in the affected protein. PolyQ fibrils have been studied in detail; however, less is known about oligomeric precursor states. By a combination of time-resolved temperature-jump (T-jump) infrared (IR) spectroscopy and an appropriately tailored polyQ model peptide, we succeeded in disentangling conformational dynamics in the heterogeneous ensemble of states evolving during aggregation. Individual structural elements could be differentiated by IR-specific signatures, i.e., hairpin monomers, β-structured oligomers, and disordered structure. Submillisecond dynamics were observed for early oligomeric states in contrast to the slow dynamics of fibril growth. We propose that a high structural flexibility of oligomers is required to initiate fibril formation, but not after a fibrillar structure has consolidated and the fibril just grows. Our study reveals that structural flexibility changes at different stages in the aggregation process, from fibril initiation to fibril growth.</dcterms:abstract>
    <dcterms:issued>2022-05-26</dcterms:issued>
    <dc:language>eng</dc:language>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-06-23T13:22:26Z</dc:date>
    <dcterms:title>Observation of Oligomeric States Indicates a High Structural Flexibility Required for the Onset of Polyglutamine Fibrillization</dcterms:title>
    <dc:creator>Siu, Ho-Wah</dc:creator>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
  </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