On How the Conformational Cycle of the AcrB Efflux Pump is Coupled to Proton Translocation : a Theoretical Study Based on High-Resolution Structural Data

Lade...
Vorschaubild
Dateien
Zu diesem Dokument gibt es keine Dateien.
Datum
2011
Autor:innen
Anselmi, Claudio
Pos, Klaas M.
Faraldo-Gómez, José D.
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
Biophysical Journal. 2011, 100(3), pp. 412a. ISSN 0006-3495. eISSN 1542-0086. Available under: doi: 10.1016/j.bpj.2010.12.2442
Zusammenfassung

The AcrA/AcrB/TolC multidrug efflux pump confers Escherichia coli with antibiotic resistance by sequestering toxic compounds found within the periplasm and inner membrane and extruding them into the extracellular space. The AcrB trimer is the central component of this efflux complex; anchored in the inner membrane, it forms an asymmetric assembly that undergoes a conformational cycle in which each protomer adopts three different structures. As a result, substrates bound in the periplasmic domain of AcrB are projected into the TolC channel, which reaches beyond the outer membrane. Crucially, the conformational cycle within AcrB is driven by the translocation of protons down the gradient sustained by the inner membrane, through a mechanism that has not been characterized so far. Here, we investigate this microscopic mechanism through atomistic freeenergy molecular dynamics simulations and electrostatic calculations, based upon novel high-resolution structural data for wild-type and mutagenized AcrB. Specifically, we assess the events associated with binding and release of protons within the membrane domain, and determine the mechanism by which these events are coupled to the reorganization of key transmembrane helices within each protomer. This investigation reveals how proton translocation influences both local and remote interactions within the protein, thereby modulating its structure.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690ANSELMI, Claudio, Wenchang ZHOU, Kay DIEDERICHS, Klaas M. POS, José D. FARALDO-GÓMEZ, 2011. On How the Conformational Cycle of the AcrB Efflux Pump is Coupled to Proton Translocation : a Theoretical Study Based on High-Resolution Structural Data. In: Biophysical Journal. 2011, 100(3), pp. 412a. ISSN 0006-3495. eISSN 1542-0086. Available under: doi: 10.1016/j.bpj.2010.12.2442
BibTex
@article{Anselmi2011-02Confo-38196,
  year={2011},
  doi={10.1016/j.bpj.2010.12.2442},
  title={On How the Conformational Cycle of the AcrB Efflux Pump is Coupled to Proton Translocation : a Theoretical Study Based on High-Resolution Structural Data},
  number={3},
  volume={100},
  issn={0006-3495},
  journal={Biophysical Journal},
  author={Anselmi, Claudio and Zhou, Wenchang and Diederichs, Kay and Pos, Klaas M. and Faraldo-Gómez, José D.}
}
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/123456789/38196">
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-03-29T09:27:19Z</dcterms:available>
    <dc:contributor>Zhou, Wenchang</dc:contributor>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/38196"/>
    <dc:creator>Faraldo-Gómez, José D.</dc:creator>
    <dc:contributor>Anselmi, Claudio</dc:contributor>
    <dc:contributor>Pos, Klaas M.</dc:contributor>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:contributor>Diederichs, Kay</dc:contributor>
    <dc:creator>Pos, Klaas M.</dc:creator>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-03-29T09:27:19Z</dc:date>
    <dc:creator>Diederichs, Kay</dc:creator>
    <dc:creator>Anselmi, Claudio</dc:creator>
    <dcterms:abstract>The AcrA/AcrB/TolC multidrug efflux pump confers Escherichia coli with antibiotic&#xD;
resistance by sequestering toxic compounds found within the periplasm&#xD;
and inner membrane and extruding them into the extracellular space. The AcrB&#xD;
trimer is the central component of this efflux complex; anchored in the inner&#xD;
membrane, it forms an asymmetric assembly that undergoes a conformational&#xD;
cycle in which each protomer adopts three different structures. As a result, substrates&#xD;
bound in the periplasmic domain of AcrB are projected into the TolC&#xD;
channel, which reaches beyond the outer membrane. Crucially, the conformational&#xD;
cycle within AcrB is driven by the translocation of protons down the gradient&#xD;
sustained by the inner membrane, through a mechanism that has not been&#xD;
characterized so far.&#xD;
Here, we investigate this microscopic mechanism through atomistic freeenergy&#xD;
molecular dynamics simulations and electrostatic calculations, based&#xD;
upon novel high-resolution structural data for wild-type and mutagenized&#xD;
AcrB. Specifically, we assess the events associated with binding and release&#xD;
of protons within the membrane domain, and determine the mechanism by&#xD;
which these events are coupled to the reorganization of key transmembrane helices&#xD;
within each protomer. This investigation reveals how proton translocation&#xD;
influences both local and remote interactions within the protein, thereby modulating&#xD;
its structure.</dcterms:abstract>
    <dc:creator>Zhou, Wenchang</dc:creator>
    <dc:contributor>Faraldo-Gómez, José D.</dc:contributor>
    <dc:language>eng</dc:language>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dcterms:title>On How the Conformational Cycle of the AcrB Efflux Pump is Coupled to Proton Translocation : a Theoretical Study Based on High-Resolution Structural Data</dcterms:title>
    <dcterms:issued>2011-02</dcterms:issued>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
  </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
Diese Publikation teilen