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An NMR Study on the Intrinsically Disordered Core Transactivation Domain of Human Glucocorticoid Receptor
Kyou-Hoon Han1,*,#, Do-Hyoung Kim1, Anthony Wright1
1Genome Editing Research Center,, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea,
2Department of Nano and Bioinformatics,, University of Science and Technology, Daejeon 34113, Korea,
3Department of Laboratory Medicine,, Clinical Research Center, Karolinska Institutet, Stockholm, Sweden
Many transcriptional activation domains (TADs) are intrinsically unstructured without a 3-D structure. The fact that such unstructured TADs are transcriptionally active raises a question on what features in these domains enable them to function. One TAD in human glucocorticoid receptor (hGR tau1c) located at its N-terminus is responsible for ~70% of the transcriptional activity of hGR. This intrinsically disordered TAD formed three helices under trifluoroethanol that might be important for its activity. We have carried out multi-dimensional NMR experiments on hGR tau1c in aqueous solution and found that it forms three helices which are ~30% pre-populated. Since the pre-populated helices in TADs are the key elements for transcriptional activity the three pre-formed helices in hGR tau1c we delineated should be the critical determinants for the transcriptional activity of hGR. Presence of pre-structured helices in hGR tau1c suggests that existence of the pre-structured motifs in target-unbound TADs is a broad phenomenon.
Abstract, Accepted Manuscript(in press) [Submitted on August 7, 2017, Accepted on September 9, 2017]
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