Acetylation and phosphorylation of TFAM have contrasting mechanisms for regulating TFAMDNA interactHashemi Shabestari, M., King, G. A., Roos, W. H., Suzuki, C. K. & Wuite, G. J. L., 1-Jul-2017, In : European Biophysics Journal. 46, Suppl. 1, p. 43-402 1 p.
Research output: Contribution to journal › Meeting Abstract › Academic
TFAM is a multifunctional protein that orchestrates mitochondrial DNA compaction, transcription and replication. While Post-translational modifications, such as TFAM phosphorylation and acetylation are thought to regulate these processes, the regulation mechanism is not understood. By single-molecule manipulation and fluorescence microscopy, we investigate the effect of TFAM phosphorylation and acetylation on DNA binding affinity. We determined the binding affinity of TFAM to DNA and the extent of TFAM induced DNA compaction. We demonstrate that phosphorylation and acetylation of TFAM do not alter its ability to compact DNA, but lower the binding affinity to DNA. Furthermore, we reveal an increase in the unbinding rate of TFAM from DNA upon phosphorylation. This indicates that the reduced binding affinity of TFAM to DNA when phosphorylated is partially due to the higher off-rate of phosphorylated TFAM. Conversely, the unbinding rate of TFAM from DNA remains unaffected by acetylation. We relate the lower binding affinity of acetylated TFAM to a decrease in the on-rate of the protein. These findings indicate that phosphorylation and acetylation can regulate TFAM function.
|Number of pages||1|
|Journal||European Biophysics Journal|
|Issue number||Suppl. 1|
|Publication status||Published - 1-Jul-2017|
- endogenous compound, acetylation, binding affinity, DNA binding, fluorescence microscopy