Elucidation of electron transfer pathways during oxidative protein folding in Escherichia coli

Bader, Martin

Elucidation of electron transfer pathways during oxidative protein folding in Escherichia coli

Dateien

Martin_Bader_Dissertation.pdfGröße: 1.64 MBDownloads: 710

Datum

2001

Autor:innen

Bader, Martin

URI (zitierfähiger Link)

http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-6647

Link zur Lizenz

Urheberrechtlich geschützt

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Titel in einer weiteren Sprache

Aufklärung des Elektronenflusses während der oxidativen Proteinfaltung in Escherichia coli

Publikationstyp

Dissertation

Publikationsstatus

Published

Zusammenfassung

Many secreted proteins require the correct formation of one or more disulfide bonds for the proper folding into their native 3-D structure. DsbA catalyzes the formation of disulfide bonds in the periplasm of E. coli. DsbA's active site disulfide bond is reoxidized by the inner membrane protein DsbB. Electrons flow from DsbA via DsbB to ubiquinone and further on to terminal cytochrome oxidase complexes, which finally transfer electrons to molecular oxygen. While growing anaerobically, E. coli replaces ubiquinones by menaquinones, which then act as mobile electron carriers between anaerobic respiratory complexes in the inner membrane. DsbB directly interacts with menaquinones suggesting a mechanism whereby DsbB drives disulfide bond formation under anaerobic conditions. The ability of DsbB to utilize alternative electron acceptors such as ubiquinones and menaquinones ensures efficient disulfide bond formation over a wide variety of growth conditions.
DsbA is a strong but non-specific oxidant leading to the complete but often incorrect oxidation of proteins. A second pathway ensures the isomerization of incorrect disulfide bonds. This pathway consists of two disulfide isomerases, DsbC and DsbG, and the inner membrane protein DsbD. DsbD is directly involved in the reduction of DsbC and DsbG by providing a link to the reducing power of the cytosol. It is puzzling how this reducing pathway can coexist with the oxidizing DsbA-DsbB system without going through futile cycles of mutual oxidation and reduction. A number of dsbC mutants were obtained which rescue a dsbA null mutant. These mutant proteins failed to dimerize and were reoxidized by DsbB in vivo and in vitro. Accordingly, DsbC seems to be protected from DsbB mediated oxidation only when present as a dimer. This is an important molecular barrier that allows the coexistence of an isomerization and oxidation pathway in the periplasm, thus securing the proper formation of disulfide bonds.

Zusammenfassung in einer weiteren Sprache

Many secreted proteins require the correct formation of one or more disulfide bonds for the proper folding into their native 3-D structure. DsbA catalyzes the formation of disulfide bonds in the periplasm of E. coli. DsbA's active site disulfide bond is reoxidized by the inner membrane protein DsbB. Electrons flow from DsbA via DsbB to ubiquinone and further on to terminal cytochrome oxidase complexes, which finally transfer electrons to molecular oxygen. While growing anaerobically, E. coli replaces ubiquinones by menaquinones, which then act as mobile electron carriers between anaerobic respiratory complexes in the inner membrane. DsbB directly interacts with menaquinones suggesting a mechanism whereby DsbB drives disulfide bond formation under anaerobic conditions. The ability of DsbB to utilize alternative electron acceptors such as ubiquinones and menaquinones ensures efficient disulfide bond formation over a wide variety of growth conditions.
DsbA is a strong but non-specific oxidant leading to the complete but often incorrect oxidation of proteins. A second pathway ensures the isomerization of incorrect disulfide bonds. This pathway consists of two disulfide isomerases, DsbC and DsbG, and the inner membrane protein DsbD. DsbD is directly involved in the reduction of DsbC and DsbG by providing a link to the reducing power of the cytosol. It is puzzling how this reducing pathway can coexist with the oxidizing DsbA-DsbB system without going through futile cycles of mutual oxidation and reduction. A number of dsbC mutants were obtained which rescue a dsbA null mutant. These mutant proteins failed to dimerize and were reoxidized by DsbB in vivo and in vitro. Accordingly, DsbC seems to be protected from DsbB mediated oxidation only when present as a dimer. This is an important molecular barrier that allows the coexistence of an isomerization and oxidation pathway in the periplasm, thus securing the proper formation of disulfide bonds.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

disulfide bond, protein folding, protein disulfide isomerase

Zitieren

ISO 690

BADER, Martin, 2001. Elucidation of electron transfer pathways during oxidative protein folding in Escherichia coli [Dissertation]. Konstanz: University of Konstanz

BibTex

@phdthesis{Bader2001Eluci-7108,
  year={2001},
  title={Elucidation of electron transfer pathways during oxidative protein folding in Escherichia coli},
  author={Bader, Martin},
  address={Konstanz},
  school={Universität Konstanz}
}

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    <dcterms:abstract xml:lang="eng">Many secreted proteins require the correct formation of one or more disulfide bonds for the proper folding into their native 3-D structure. DsbA catalyzes the formation of disulfide bonds in the periplasm of E. coli. DsbA's active site disulfide bond is reoxidized by the inner membrane protein DsbB. Electrons flow from DsbA via DsbB to ubiquinone and further on to terminal cytochrome oxidase complexes, which finally transfer electrons to molecular oxygen. While growing anaerobically, E. coli replaces ubiquinones by menaquinones, which then act as mobile electron carriers between anaerobic respiratory complexes in the inner membrane. DsbB directly interacts with menaquinones suggesting a mechanism whereby DsbB drives disulfide bond formation under anaerobic conditions. The ability of DsbB to utilize alternative electron acceptors such as ubiquinones and menaquinones ensures efficient disulfide bond formation over a wide variety of growth conditions.&lt;br /&gt;DsbA is a strong but non-specific oxidant leading to the complete but often incorrect oxidation of proteins. A second pathway ensures the isomerization of incorrect disulfide bonds. This pathway consists of two disulfide isomerases, DsbC and DsbG, and the inner membrane protein DsbD. DsbD is directly involved in the reduction of DsbC and DsbG by providing a link to the reducing power of the cytosol. It is puzzling how this reducing pathway can coexist with the oxidizing DsbA-DsbB system without going through futile cycles of mutual oxidation and reduction. A number of dsbC mutants were obtained which rescue a dsbA null mutant. These mutant proteins failed to dimerize and were reoxidized by DsbB in vivo and in vitro. Accordingly, DsbC seems to be protected from DsbB mediated oxidation only when present as a dimer. This is an important molecular barrier that allows the coexistence of an isomerization and oxidation pathway in the periplasm, thus securing the proper formation of disulfide bonds.</dcterms:abstract>
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Prüfungsdatum der Dissertation

May 21, 2001