Abstract

 

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.