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http://dx.doi.org/10.5483/BMBRep.2017.50.10.152

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)
Publication Information
BMB Reports / v.50, no.10, 2017 , pp. 522-527 More about this Journal
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.
Keywords
Human glucocorticoid receptor (hGR); Intrinsically disordered protein (IDP); Nuclear magnetic resonance (NMR); Pre-structured motif (PreSMo);
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