Interaction of an IκBα Peptide with 14-3-3.


Journal

ACS omega
ISSN: 2470-1343
Titre abrégé: ACS Omega
Pays: United States
ID NLM: 101691658

Informations de publication

Date de publication:
17 Mar 2020
Historique:
received: 22 12 2019
accepted: 19 02 2020
entrez: 24 3 2020
pubmed: 24 3 2020
medline: 24 3 2020
Statut: epublish

Résumé

Inflammatory responses mediated by the transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) play key roles in immunity, autoimmune diseases, and cancer. NF-κB is directly regulated through protein-protein interactions, including those with IκB and 14-3-3 proteins. These two important regulatory proteins have been reported to interact with each other, although little is known about this interaction. We analyzed the inhibitor of nuclear factor kappa B α (IκBα)/14-3-3σ interaction via a peptide/protein-based approach. Structural data were acquired via X-ray crystallography, while binding affinities were measured with fluorescence polarization assays and time-resolved tryptophan fluorescence. A high-resolution crystal structure (1.13 Å) of the uncommon 14-3-3 interaction motif of IκBα (IκBαpS63) in a complex with 14-3-3σ was evaluated. This motif harbors a tryptophan that makes this crystal structure the first one with such a residue visible in the electron density at that position. We used this tryptophan to determine the binding affinity of the unlabeled IκBα peptide to 14-3-3 via tryptophan fluorescence decay measurements.

Identifiants

pubmed: 32201828
doi: 10.1021/acsomega.9b04413
pmc: PMC7081424
doi:

Types de publication

Journal Article

Langues

eng

Pagination

5380-5388

Informations de copyright

Copyright © 2020 American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

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Auteurs

Madita Wolter (M)

Department of Biomedical Engineering, Laboratory of Chemical Biology and Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.

Domenico Lentini Santo (DL)

Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Prague 12843, Czech Republic.

Petr Herman (P)

Institute of Physics, Faculty of Mathematics and Physics, Charles University, Prague 12116, Czech Republic.

Alice Ballone (A)

Department of Biomedical Engineering, Laboratory of Chemical Biology and Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.

Federica Centorrino (F)

Department of Biomedical Engineering, Laboratory of Chemical Biology and Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.

Tomas Obsil (T)

Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Prague 12843, Czech Republic.

Christian Ottmann (C)

Department of Biomedical Engineering, Laboratory of Chemical Biology and Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
Department of Organic Chemistry, University of Duisburg-Essen, 45117 Essen, Germany.

Classifications MeSH