Structural Basis for the Interaction between p53 Transactivation Domain and the Mediator Subunit MED25.
Min-Sung LeeKyungeun LimMi-Kyung LeeSeung-Wook ChiPublished in: Molecules (Basel, Switzerland) (2018)
Eukaryotic transcription initiation is mediated by interactions between transcriptional activators and the mediator coactivator complex. Molecular interaction of p53 transcription factor with mediator complex subunit 25 (MED25) is essential for its target gene transcription. In this study, we characterized the molecular interaction between p53 transactivation domain (p53TAD) and activator interaction domain (ACID) of MED25 using nuclear magnetic resonance (NMR) spectroscopy. The NMR chemical shift perturbation and isothermal titration calorimetry (ITC) data showed that p53TAD interacted with MED25 ACID mainly through the p53TAD2 sequence motif. Taken together with the mutagenesis data, the refined structural model of MED25 ACID/p53TAD2 peptide complex showed that an amphipathic α-helix of p53TAD2 peptide bound an elongated hydrophobic groove of MED25 ACID. Furthermore, our results revealed the highly conserved mechanism of MED25 interaction with intrinsically unfolded acidic TADs from the transcriptional activators p53, ERM (Ets-related molecule), and herpes simplex virus protein 16 (VP16).
Keyphrases
- transcription factor
- magnetic resonance
- dna binding
- herpes simplex virus
- structural basis
- gene expression
- genome wide identification
- electronic health record
- big data
- ionic liquid
- high resolution
- genome wide
- immune response
- protein kinase
- computed tomography
- magnetic resonance imaging
- endoplasmic reticulum stress
- data analysis
- mass spectrometry
- heat shock