کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5371242 | 1503943 | 2012 | 5 صفحه PDF | دانلود رایگان |
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-1Â +Â H2 and HI-1Â +Â 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.
Highlights⺠Simulation of Ets-1 constructs identified how HI-1 is stabilized in the apo state. ⺠Contacts between HI-1 and HI-2/H4 are important for the stability of HI-1. ⺠Removal of a few local contacts may lead to the partial unfolding of Ets-1.
Journal: Biophysical Chemistry - Volumes 165â166, May 2012, Pages 74-78