Imperial College London
Alternate

DrRobertWeinzierl

Faculty of Natural Sciences, Department of Life Sciences

Reader in Molecular Biology
 
 
 
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Contact

 

+44 (0)20 7594 5236r.weinzierl

 
 
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Location

 

510Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Weinzierl:2020:10.3390/biom10091205,
author = {Weinzierl, R and Jeffery, H and Weinzierl, R},
doi = {10.3390/biom10091205},
journal = {Biomolecules},
title = {Multivalent and bidirectional binding of transcriptional transactivation domains to the MED25 coactivator},
url = {http://dx.doi.org/10.3390/biom10091205},
volume = {9},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The human mediator subunit MED25 acts as a coactivator that binds the transcriptional activation domains (TADs) present in various cellular and viral gene-specific transcription factors. Previous studies, including on NMR measurements and site-directed mutagenesis, have only yielded low-resolution models that are difficult to refine further by experimental means. Here, we apply computational molecular dynamics simulations to study the interactions of two different TADs from the human transcription factor ETV5 (ERM) and Herpes virus VP16-H1 with MED25. Like other well-studied coactivator-TAD complexes, the interactions of these intrinsically disordered domains with the coactivator surface are temporary and highly dynamic (‘fuzzy’). Due to the fact that the MED25 TAD-binding region is organized as an elongated cleft, we specifically asked whether these TADs are capable of binding in either orientation and how this could be achieved structurally and energetically. Binding of both the ETV5 and VP16-TADs in either orientation appears to be possible but occurs in a conformationally distinct manner and utilizes different sets of hydrophobic residues present in the TADs to drive the interactions. We propose that MED25 and at least a subset of human TADs specifically evolved a redundant set of molecular interaction patterns to allow binding to particular coactivator binding without major prior spatial constraints.
AU  - Weinzierl,R
AU  - Jeffery,H
AU  - Weinzierl,R
DO  - 10.3390/biom10091205
PY  - 2020///
SN  - 2218-273X
TI  - Multivalent and bidirectional binding of transcriptional transactivation domains to the MED25 coactivator
T2  - Biomolecules
UR  - http://dx.doi.org/10.3390/biom10091205
UR  - http://hdl.handle.net/10044/1/82333
VL  - 9
ER  -
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