A model for dimerization of the SOX Group E transcription factor family

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dc.contributor.authorDonaldson, Logan
dc.date.accessioned2016-04-22T22:01:14Z
dc.date.available2016-04-22T22:01:14Z
dc.date.issued2016-04-22
dc.description.abstractGroup 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. From a mutagenic scan of the dimerization region, the most essential amino acids 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 explains how variable spacing between binding sites and different DNA bending angles can be accommodated through the participation of an unstructured linker region between the dimerization-specific helix and the HMG domain. Furthermore, the model provides a basis to explain why the A76E mutation in the dimerization region of human SOX9 is responsible for campomelic dysplasia, a disease associated with major limb and reproductive defects
dc.description.sponsorshipNatural Sciences and Engineering Research Council of Canada (NSERC) funded project to LWDen
dc.identifier.urihttp://hdl.handle.net/10315/31187
dc.language.isoenen
dc.rightsCC0 1.0 Universal*
dc.rightsCC0 1.0 Universal*
dc.rights.journalhttp://www.plosone.orgen_US
dc.rights.publisherhttp://www.plos.orgen
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.subjectMolecular modelen
dc.subjectProtein-DNA interactionen
dc.subjectMolecular modelen_US
dc.subjectProtein-DNA interactionen_US
dc.titleA model for dimerization of the SOX Group E transcription factor familyen
dc.typeImage, 3-Den

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