4.7 Article

Triiodothyronine Acts as a Smart Influencer on Hsp90 via a Triiodothyronine Binding Site

Journal

Publisher

MDPI
DOI: 10.3390/ijms23137150

Keywords

triiodothyronine; Hsp90; protein microarray; thermophoresis; molecular docking

Funding

  1. FOR 5170: CytoLabs-Systematic Investigation and Exploitation of Cytochalasans [ZE 338/16-1]
  2. DFG Cluster of Excellence EXC 2177/1 Hearing4all

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Microarray-based experiments showed that thyroid hormone T3 enhanced the binding of Cy5-labeled ATP on Hsp90. Molecular docking experiments identified a T3 binding site near the ATP binding site on Hsp90. A synthetic peptide derived from this binding site displayed T3 binding ability in experiments.
Microarray-based experiments revealed that thyroid hormone triiodothyronine (T3) enhanced the binding of Cy5-labeled ATP on heat shock protein 90 (Hsp90). By molecular docking experiments with T3 on Hsp90, we identified a T3 binding site (TBS) near the ATP binding site on Hsp90. A synthetic peptide encoding HHHHHHRIKEIVKKHSQFIGYPITLFVEKE derived from the TBS on Hsp90 showed, in MST experiments, the binding of T3 at an EC50 of 50 mu M. The binding motif can influence the activity of Hsp90 by hindering ATP accessibility or the release of ADP.

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