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- Title
DNA binding reduces the dissociation rate of ST ATI dimers and impairs the interdimeric exchange of protomers.
- Authors
Riebeling, Theresa; Staab, Julia; Herrmann-Lingen, Christoph; Meyer, Thomas
- Abstract
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-y (IFNy)-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 (gammaactivated 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 IFNy-mediated signal transduction. Further investigations are needed to decipher the physiological significance of the observed dissociation/reassociation process of STAT1 dimers.
- Subjects
DNA-binding proteins; STAT proteins; DIMERS; INTERFERON gamma; GENETIC transcription; CELLULAR signal transduction
- Publication
BMC Biochemistry, 2014, Vol 15, Issue 1, p82
- ISSN
1471-2091
- Publication type
Article
- DOI
10.1186/s12858-014-0028-z