An NMR study on the intrinsically disordered core transactivation domain of human glucocorticoid receptor

作者：Kim Do Hyoung; Wright Anthony; Han Kyou Hoon^*

来源：BMB Reports, 2017, 50(10): 522-527.

DOI：10.5483/BMBRep.2017.50.10.152

• Human glucocorticoid receptor (hGR)
• Intrinsically disordered protein (IDP)
• Nuclear magnetic resonance (NMR)
• Pre-structured motif (PreSMo)

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 similar to 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 similar to 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.

• 出版日期2017