Imperial College London
Portrait Picture

ProfessorIanGould

Faculty of Natural Sciences, Department of Chemistry

Senior Research Investigator
 
 
 
//

Contact

 

+44 (0)20 7594 5809i.gould

 
 
//

Location

 

110BMolecular Sciences Research HubWhite City Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Beuerle:2016:10.1039/c6mb00506c,
author = {Beuerle, MG and Dufton, NP and Randi, AM and Gould, IR},
doi = {10.1039/c6mb00506c},
journal = {Molecular BioSystems},
pages = {3600--3610},
title = {Molecular dynamics studies on the DNA-binding process of ERG},
url = {http://dx.doi.org/10.1039/c6mb00506c},
volume = {12},
year = {2016}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The ETS family of transcription factors regulate gene targets by binding to a core GGAA DNA-sequence. The ETS factor ERG is required for homeostasis and lineage-specific functions in endothelial cells, some subset of haemopoietic cells and chondrocytes; its ectopic expression is linked to oncogenesis in multiple tissues. To date details of the DNA-binding process of ERG including DNA-sequence recognition outside the core GGAA-sequence are largely unknown. We combined available structural and experimental data to perform molecular dynamics simulations to study the DNA-binding process of ERG. In particular we were able to reproduce the ERG DNA-complex with a DNA-binding simulation starting in an unbound configuration with a final root-mean-square-deviation (RMSD) of 2.1 Å to the core ETS domain DNA-complex crystal structure. This allowed us to elucidate the relevance of amino acids involved in the formation of the ERG DNA-complex and to identify Arg385 as a novel key residue in the DNA-binding process. Moreover we were able to show that water-mediated hydrogen bonds are present between ERG and DNA in our simulations and that those interactions have the potential to achieve sequence recognition outside the GGAA core DNA-sequence. The methodology employed in this study shows the promising capabilities of modern molecular dynamics simulations in the field of protein DNA-interactions.
AU  - Beuerle,MG
AU  - Dufton,NP
AU  - Randi,AM
AU  - Gould,IR
DO  - 10.1039/c6mb00506c
EP  - 3610
PY  - 2016///
SN  - 1742-206X
SP  - 3600
TI  - Molecular dynamics studies on the DNA-binding process of ERG
T2  - Molecular BioSystems
UR  - http://dx.doi.org/10.1039/c6mb00506c
UR  - http://hdl.handle.net/10044/1/41451
VL  - 12
ER  -
Download