The Transcriptional Repressor Domain of Gli3 Is Intrinsically Disordered |
| |
| Authors: | Robert Tsanev Kalju Vanatalu Jüri Jarvet Risto Tanner Kristi Laur Piret Tiigim?gi Birthe B. Kragelund Torben ?sterlund Priit Kogerman |
| |
| Affiliation: | 1. Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia.; 2. National Institute of Chemical Physics and Biophysics, Tallinn, Estonia.; 3. Structural Biology and Nuclear Magnetic Resonance Laboratory, University of Copenhagen, Copenhagen, Denmark.; 4. Molecular Pharmacology, Zealand Pharma A/S, Glostrup, Denmark.; University of South Florida College of Medicine, United States of America, |
| |
| Abstract: | The transcription factor Gli3 is acting mainly as a transcriptional repressor in the Sonic hedgehog signal transduction pathway. Gli3 contains a repressor domain in its N-terminus from residue G106 to E236. In this study we have characterized the intracellular structure of the Gli3 repressor domain using a combined bioinformatics and experimental approach. According to our findings the Gli3 repressor domain while being intrinsically disordered contains predicted anchor sites for partner interactions. The obvious interaction partners to test were Ski and DNA; however, with both of these the structure of Gli3 repressor domain remained disordered. To locate residues important for the repressor function we mutated several residues within the Gli3 repressor domain. Two of these, H141A and H157N, targeting predicted helical regions, significantly decreased transcriptional repression and thus identify important functional parts of the domain. |
| |
| Keywords: | |
|
|
