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DNA binding reduces the dissociation rate of STAT1 dimers and impairs the interdimeric exchange of protomers
BACKGROUND: A shift between two dimer conformations has been proposed for the transcription factor STAT1 (signal transducer and activator of transcription 1) which links DNA binding of the parallel dimer to tyrosine dephosphorylation of the antiparallel dimer as two consecutive and important steps i...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284922/ https://www.ncbi.nlm.nih.gov/pubmed/25526807 http://dx.doi.org/10.1186/s12858-014-0028-z |
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author | Riebeling, Theresa Staab, Julia Herrmann-Lingen, Christoph Meyer, Thomas |
author_facet | Riebeling, Theresa Staab, Julia Herrmann-Lingen, Christoph Meyer, Thomas |
author_sort | Riebeling, Theresa |
collection | PubMed |
description | BACKGROUND: A shift between two dimer conformations has been proposed for the transcription factor STAT1 (signal transducer and activator of transcription 1) which links DNA binding of the parallel dimer to tyrosine dephosphorylation of the antiparallel dimer as two consecutive and important steps in interferon- γ (IFNγ)-mediated signalling. However, neither the kinetics nor the molecular mechanisms involved in this conformational transition have been determined so far. RESULTS: Our results demonstrated that the dissociation of dimers into monomers and their subsequent re-association into newly formed tyrosine-phosphorylated dimers is a relatively slow process as compared to the fast release from high-affinity DNA-binding sites, termed GAS (gamma-activated sequence). In addition, we noted an inhibitory effect of GAS binding on the exchange rate of protomers, indicating that DNA binding substantially impedes the recombination of dimeric STAT1. Furthermore, we found that reciprocal aminoterminal interactions between two STAT1 molecules are not required for the interchange of protomers, as an oligomerization-deficient point mutant displayed similar interdimeric exchange kinetics as the wild-type molecule. CONCLUSIONS: Our results demonstrate that DNA binding impairs the oscillation rate between STAT1 conformers. Furthermore, these data suggest that the rapid release from high-affinity GAS sites is not a rate-limiting step in IFNγ-mediated signal transduction. Further investigations are needed to decipher the physiological significance of the observed dissociation/re-association process of STAT1 dimers. |
format | Online Article Text |
id | pubmed-4284922 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42849222015-01-07 DNA binding reduces the dissociation rate of STAT1 dimers and impairs the interdimeric exchange of protomers Riebeling, Theresa Staab, Julia Herrmann-Lingen, Christoph Meyer, Thomas BMC Biochem Research Article BACKGROUND: A shift between two dimer conformations has been proposed for the transcription factor STAT1 (signal transducer and activator of transcription 1) which links DNA binding of the parallel dimer to tyrosine dephosphorylation of the antiparallel dimer as two consecutive and important steps in interferon- γ (IFNγ)-mediated signalling. However, neither the kinetics nor the molecular mechanisms involved in this conformational transition have been determined so far. RESULTS: Our results demonstrated that the dissociation of dimers into monomers and their subsequent re-association into newly formed tyrosine-phosphorylated dimers is a relatively slow process as compared to the fast release from high-affinity DNA-binding sites, termed GAS (gamma-activated sequence). In addition, we noted an inhibitory effect of GAS binding on the exchange rate of protomers, indicating that DNA binding substantially impedes the recombination of dimeric STAT1. Furthermore, we found that reciprocal aminoterminal interactions between two STAT1 molecules are not required for the interchange of protomers, as an oligomerization-deficient point mutant displayed similar interdimeric exchange kinetics as the wild-type molecule. CONCLUSIONS: Our results demonstrate that DNA binding impairs the oscillation rate between STAT1 conformers. Furthermore, these data suggest that the rapid release from high-affinity GAS sites is not a rate-limiting step in IFNγ-mediated signal transduction. Further investigations are needed to decipher the physiological significance of the observed dissociation/re-association process of STAT1 dimers. BioMed Central 2014-12-20 /pmc/articles/PMC4284922/ /pubmed/25526807 http://dx.doi.org/10.1186/s12858-014-0028-z Text en © Riebeling et al.; licensee BioMed Central. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Riebeling, Theresa Staab, Julia Herrmann-Lingen, Christoph Meyer, Thomas DNA binding reduces the dissociation rate of STAT1 dimers and impairs the interdimeric exchange of protomers |
title | DNA binding reduces the dissociation rate of STAT1 dimers and impairs the interdimeric exchange of protomers |
title_full | DNA binding reduces the dissociation rate of STAT1 dimers and impairs the interdimeric exchange of protomers |
title_fullStr | DNA binding reduces the dissociation rate of STAT1 dimers and impairs the interdimeric exchange of protomers |
title_full_unstemmed | DNA binding reduces the dissociation rate of STAT1 dimers and impairs the interdimeric exchange of protomers |
title_short | DNA binding reduces the dissociation rate of STAT1 dimers and impairs the interdimeric exchange of protomers |
title_sort | dna binding reduces the dissociation rate of stat1 dimers and impairs the interdimeric exchange of protomers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284922/ https://www.ncbi.nlm.nih.gov/pubmed/25526807 http://dx.doi.org/10.1186/s12858-014-0028-z |
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