A Model for Dimerization of the SOX Group E Transcription Factor Family

• Published in: PloS one 2016-08, Vol.11 (8), p.e0161432
• Main Authors: Ramsook, Sarah N, Ni, Joyce, Shahangian, Shokofeh, Vakiloroayaei, Ana, Khan, Naveen, Kwan, Jamie J, Donaldson, Logan W
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino Acid Substitution - genetics; Amino acids; Binding sites; Binding Sites - genetics; Biology and life sciences; Conservation; Conserved sequence; Crystallography; Deoxyribonucleic acid; Dimerization; Dimers; DNA; DNA-Binding Proteins - metabolism; Electrophoretic Mobility Shift Assay; High mobility group proteins; HMG-Box Domains - genetics; Humans; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; Hypotheses; Integrated software; Models, Molecular; Molecular biology; Molecular Docking Simulation; Mutagenesis; Mutation; Nucleotide sequence; Physical Sciences; Physiological aspects; Promoter Regions, Genetic; Protein Multimerization - genetics; Proteins; Research and Analysis Methods; Sox10 protein; Sox9 protein; SOX9 Transcription Factor - genetics; SOX9 Transcription Factor - metabolism; Transcription factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0161432

Group E members of the SOX transcription factor family include SOX8, SOX9, and SOX10. Preceding the high mobility group (HMG) domain in each of these proteins is a thirty-eight amino acid region that supports the formation of dimers on promoters containing tandemly inverted sites. The purpose of this study was to obtain new structural insights into how the dimerization region functions with the HMG domain. From a mutagenic scan of the dimerization region, the most essential amino acids of the dimerization region were clustered on the hydrophobic face of a single, predicted amphipathic helix. Consistent with our hypothesis that the dimerization region directly contacts the HMG domain, a peptide corresponding to the dimerization region bound a preassembled HMG-DNA complex. Sequence conservation among Group E members served as a basis to identify two surface exposed amino acids in the HMG domain of SOX9 that were necessary for dimerization. These data were combined to make a molecular model that places the dimerization region of one SOX9 protein onto the HMG domain of another SOX9 protein situated at the opposing site of a tandem promoter. The model provides a detailed foundation for assessing the impact of mutations on SOX Group E transcription factors.