Structural Basis for the Interaction between p53 Transactivation Domain and the Mediator Subunit MED25
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 charac...
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| Format: | Article |
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MDPI AG
2018-10-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/23/10/2726 |
| _version_ | 1818538764031492096 |
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| author | Min-Sung Lee Kyungeun Lim Mi-Kyung Lee Seung-Wook Chi |
| author_facet | Min-Sung Lee Kyungeun Lim Mi-Kyung Lee Seung-Wook Chi |
| author_sort | Min-Sung Lee |
| collection | DOAJ |
| description | 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). |
| first_indexed | 2024-12-11T21:33:11Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T21:33:11Z |
| publishDate | 2018-10-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-720dedb4bdb54bd8a56ec2a39646b2392022-12-22T00:50:06ZengMDPI AGMolecules1420-30492018-10-012310272610.3390/molecules23102726molecules23102726Structural Basis for the Interaction between p53 Transactivation Domain and the Mediator Subunit MED25Min-Sung Lee0Kyungeun Lim1Mi-Kyung Lee2Seung-Wook Chi3Disease Target Structure Research Center, KRIBB, Daejeon 34141, KoreaDisease Target Structure Research Center, KRIBB, Daejeon 34141, KoreaDisease Target Structure Research Center, KRIBB, Daejeon 34141, KoreaDisease Target Structure Research Center, KRIBB, Daejeon 34141, KoreaEukaryotic 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).http://www.mdpi.com/1420-3049/23/10/2726p53MED25transactivation domainprotein-protein interactioncomplex structurenuclear magnetic resonance |
| spellingShingle | Min-Sung Lee Kyungeun Lim Mi-Kyung Lee Seung-Wook Chi Structural Basis for the Interaction between p53 Transactivation Domain and the Mediator Subunit MED25 Molecules p53 MED25 transactivation domain protein-protein interaction complex structure nuclear magnetic resonance |
| title | Structural Basis for the Interaction between p53 Transactivation Domain and the Mediator Subunit MED25 |
| title_full | Structural Basis for the Interaction between p53 Transactivation Domain and the Mediator Subunit MED25 |
| title_fullStr | Structural Basis for the Interaction between p53 Transactivation Domain and the Mediator Subunit MED25 |
| title_full_unstemmed | Structural Basis for the Interaction between p53 Transactivation Domain and the Mediator Subunit MED25 |
| title_short | Structural Basis for the Interaction between p53 Transactivation Domain and the Mediator Subunit MED25 |
| title_sort | structural basis for the interaction between p53 transactivation domain and the mediator subunit med25 |
| topic | p53 MED25 transactivation domain protein-protein interaction complex structure nuclear magnetic resonance |
| url | http://www.mdpi.com/1420-3049/23/10/2726 |
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