title: Importance of local interactions for the stability of inhibitory helix 1 in apo Ets-1.
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.
authors.affiliation: Department of Chemistry, University of South Florida, 4202 East Fowler Avenue CHE 205, Tampa, FL 33620, USA.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Karolak
authors.forename: Arjan
authors.initials: A
authors.lastname: van der Vaart
mesh_terms: D001059:Apoproteins / Q000737:chemistry* / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D050784:Proto-Oncogene Protein c-ets-1 / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D001059:Apoproteins; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D004247:DNA