The transcriptional repressor domain of Gli3 is intrinsically disordered

TY - JOUR

T1 - The transcriptional repressor domain of Gli3 is intrinsically disordered

AU - Tsanev, Robert

AU - Vanatalu, Kalju

AU - Jarvet, Jüri

AU - Tanner, Risto

AU - Laur, Kristi

AU - Tiigimägi, Piret

AU - Kragelund, Birthe Brandt

AU - Østerlund, Torben

AU - Kogerman, Priit

PY - 2013/10/17

Y1 - 2013/10/17

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Cell Line

KW - DNA-Binding Proteins

KW - Humans

KW - Intrinsically Disordered Proteins

KW - Kruppel-Like Transcription Factors

KW - Mutation

KW - Nerve Tissue Proteins

KW - Nuclear Magnetic Resonance, Biomolecular

KW - Protein Binding

KW - Protein Interaction Domains and Motifs

KW - Proto-Oncogene Proteins

KW - Recombinant Fusion Proteins

KW - Repressor Proteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1371/journal.pone.0076972

DO - 10.1371/journal.pone.0076972

M3 - Journal article

C2 - 24146948

SN - 1932-6203

VL - 8

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 10

M1 - e76972

ER -