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Updated: Aug 3, 2026
09:58
Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
Conformations and dynamics of Ets-1 ETS domain-DNA complexes
Swarnalatha Y Reddy1, Satoshi Obika, Thomas C Bruice
1Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, USA.
Summary
Molecular dynamics simulations reveal that a single mutation in the Ets-1 transcription factor
Area of Science:
- Biochemistry
- Structural Biology
- Computational Biology
Background:
- Ets-1 is a transcription factor crucial for gene regulation.
- Its DNA-binding domain recognizes specific DNA sequences, including the high-affinity GGAA core motif.
- Understanding the structural dynamics of Ets-1-DNA interactions is key to deciphering transcription regulation.
Purpose of the Study:
- To investigate the molecular dynamics of the Ets-1 transcription factor bound to both high-affinity (ETS-GGAA) and low-affinity (ETS-GGAG) DNA sequences.
- To elucidate how a single nucleotide mutation affects DNA conformation, protein-DNA interactions, and water dynamics.
Main Methods:
- Molecular dynamics (MD) simulations were performed on the ETS domain of Ets-1 complexed with two different DNA sequences.
- Simulations were conducted for 3.5 ns (ETS-GGAA) and 3.9 ns (ETS-GGAG).
- Analyses included DNA backbone conformation, helical parameters, solvent accessibility, water dynamics, and protein amino acid motions.
Main Results:
- The low-affinity ETS-GGAG DNA exhibited conformational interconversions (BI to BII) and crankshaft motions, unlike the stable BI conformation of ETS-GGAA.
- The mutation altered DNA helical parameters and solvent-accessible surface area.
- Water molecules showed distinct mobility patterns around the DNA in ETS-GGAA versus ETS-GGAG.
- Anticorrelated motions between Ets-1 amino acids were prominent in ETS-GGAA but reduced in ETS-GGAG.
Conclusions:
- The study highlights significant conformational differences between high-affinity and low-affinity Ets-1-DNA complexes.
- Conformational flexibility and specific water contacts appear to stabilize Ets-1-DNA hydrogen bonds during transcription.
- These findings provide insights into the molecular mechanisms underlying transcription factor binding affinity and gene regulation.
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