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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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An NMR study on the intrinsically disordered core transactivation domain of human glucocorticoid receptor

  • Kim, Do-Hyoung (Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Wright, Anthony (Clinical Research Center, Department of Laboratory Medicine, Karolinska Institute) ;
  • Han, Kyou-Hoon (Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2017.08.07
  • Accepted : 2017.09.09
  • Published : 2017.10.31
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Abstract

A large number of transcriptional activation domains (TADs) are intrinsically unstructured, meaning they are devoid of a three-dimensional structure. The fact that these TADs are transcriptionally active without forming a 3-D structure raises the question of what features in these domains enable them to function. One of two TADs in human glucocorticoid receptor (hGR) is located at its N-terminus and is responsible for ~70% of the transcriptional activity of hGR. This 58-residue intrinsically-disordered TAD, named tau1c in an earlier study, was shown to form three helices under trifluoroethanol, which might be important for its activity. We carried out heteronuclear multi-dimensional NMR experiments on hGR tau1c in a more physiological aqueous buffer solution and found that it forms three helices that are ~30% pre-populated. Since pre-populated helices in several TADs were shown to be key elements for transcriptional activity, the three pre-formed helices in hGR tau1c delineated in this study should be critical determinants of the transcriptional activity of hGR. The presence of pre-structured helices in hGR tau1c strongly suggests that the existence of pre-structured motifs in target-unbound TADs is a very broad phenomenon.

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