Importance of local interactions for the stability of inhibitory helix 1 in apo Ets-1
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Updated: May 23, 2026

Single-Molecule Measurement of Protein Interaction Dynamics Within Biomolecular Condensates
Published on: January 5, 2024
Aleksandra Karolak1, Arjan van der Vaart
1Department of Chemistry, University of South Florida, 4202 East Fowler Avenue CHE 205, Tampa, FL 33620, USA.
Abstract:
Inhibitory helix 1 (HI-1) of the Ets-1 human transcription factor unfolds upon binding the target DNA sequence. To identify the interactions that stabilize HI-1 in the apo state, we performed replica exchange and molecular dynamics simulations of various apo Ets-1 constructs. The simulations indicate the importance of local interactions for the stability of HI-1. The HI-2 and H4 helices stabilize the helical state of HI-1 through specific residue-residue contacts and macrodipolar interactions. The amount of stabilization in small length HI-1+H2 and HI-1+H4 constructs was similar to that in the protein. The studies suggest that the partial unfolding of Ets-1 upon DNA binding can be achieved by the removal of just a few specific local contacts.
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