title: A Model for Dimerization of the SOX Group E Transcription Factor Family.
abstract: 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.
authors.affiliation: Department of Biology, York University, Toronto, ON, Canada.
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Ramsook
authors.affiliation: Department of Biology, York University, Toronto, ON, Canada.
authors.forename: Joyce
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Biology, York University, Toronto, ON, Canada.
authors.forename: Shokofeh
authors.initials: S
authors.lastname: Shahangian
authors.affiliation: Department of Biology, York University, Toronto, ON, Canada.
authors.forename: Ana
authors.initials: A
authors.lastname: Vakiloroayaei
authors.affiliation: Department of Biology, York University, Toronto, ON, Canada.
authors.forename: Naveen
authors.initials: N
authors.lastname: Khan
authors.affiliation: Department of Biology, York University, Toronto, ON, Canada.
authors.forename: Jamie J
authors.initials: JJ
authors.lastname: Kwan
authors.affiliation: Department of Biology, York University, Toronto, ON, Canada.
authors.forename: Logan W
authors.identifier: http://orcid.org/0000-0001-5034-2699
authors.initials: LW
authors.lastname: Donaldson
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D024202:Electrophoretic Mobility Shift Assay; D024742:HMG-Box Domains / Q000235:genetics*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011401:Promoter Regions, Genetic; D055503:Protein Multimerization / Q000235:genetics*; D055758:SOX9 Transcription Factor / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human