KMID : 0624620170500100522
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BMB Reports 2017 Volume.50 No. 10 p.522 ~ p.527
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An NMR study on the intrinsically disordered core transactivation domain of human glucocorticoid receptor
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Kim Do-Hyoung
Wright Anthony Han Kyou-Hoon
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Abstract
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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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KEYWORD
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Human glucocorticoid receptor (hGR), Intrinsically disordered protein (IDP), Nuclear magnetic resonance (NMR), Pre-structured motif (PreSMo)
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