Assessment of machine-learning predictions for the Mediator complex subunit MED25 ACID domain interactions with transactivation domains
© 2024 Federation of European Biochemical Societies..
The human Mediator complex subunit MED25 binds transactivation domains (TADs) present in various cellular and viral proteins using two binding interfaces, named H1 and H2, which are found on opposite sides of its ACID domain. Here, we use and compare deep learning methods to characterize human MED25-TAD interfaces and assess the predicted models to published experimental data. For the H1 interface, AlphaFold produces predictions with high-reliability scores that agree well with experimental data, while the H2 interface predictions appear inconsistent, preventing reliable binding modes. Despite these limitations, we experimentally assess the validity of MED25 interface predictions with the viral transcriptional activators Lana-1 and IE62. AlphaFold predictions also suggest the existence of a unique hydrophobic pocket for the Arabidopsis MED25 ACID domain.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:598 |
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| Enthalten in: |
FEBS letters - 598(2024), 7 vom: 01. Apr., Seite 758-773 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Monté, Didier [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.04.2024 Date Revised 09.04.2024 published: Print-Electronic RefSeq: X04370.1 Citation Status MEDLINE |
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| doi: |
10.1002/1873-3468.14837 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369260155 |
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| 245 | 1 | 0 | |a Assessment of machine-learning predictions for the Mediator complex subunit MED25 ACID domain interactions with transactivation domains |
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| 500 | |a Date Revised 09.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a RefSeq: X04370.1 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 Federation of European Biochemical Societies. | ||
| 520 | |a The human Mediator complex subunit MED25 binds transactivation domains (TADs) present in various cellular and viral proteins using two binding interfaces, named H1 and H2, which are found on opposite sides of its ACID domain. Here, we use and compare deep learning methods to characterize human MED25-TAD interfaces and assess the predicted models to published experimental data. For the H1 interface, AlphaFold produces predictions with high-reliability scores that agree well with experimental data, while the H2 interface predictions appear inconsistent, preventing reliable binding modes. Despite these limitations, we experimentally assess the validity of MED25 interface predictions with the viral transcriptional activators Lana-1 and IE62. AlphaFold predictions also suggest the existence of a unique hydrophobic pocket for the Arabidopsis MED25 ACID domain | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AlphaFold | |
| 650 | 4 | |a machine learning | |
| 650 | 4 | |a mediator complex | |
| 650 | 4 | |a transactivation domain | |
| 650 | 7 | |a Mediator Complex |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a MED25 protein, human |2 NLM | |
| 650 | 7 | |a IE62 protein, Human herpesvirus 3 |2 NLM | |
| 650 | 7 | |a Viral Envelope Proteins |2 NLM | |
| 650 | 7 | |a Trans-Activators |2 NLM | |
| 650 | 7 | |a Immediate-Early Proteins |2 NLM | |
| 700 | 1 | |a Lens, Zoé |e verfasserin |4 aut | |
| 700 | 1 | |a Dewitte, Frédérique |e verfasserin |4 aut | |
| 700 | 1 | |a Villeret, Vincent |e verfasserin |4 aut | |
| 700 | 1 | |a Verger, Alexis |e verfasserin |4 aut | |
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