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

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

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Title: A model for dimerization of the SOX Group E transcription factor family,
Author: Donaldson, Logan W
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. 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
Sponsor: Natural Sciences and Engineering Research Council of Canada (NSERC) funded project to LWD
Subject: Molecular model, protein-DNA interaction
Type: Image, 3-D
Rights: CC0 1.0 Universal CC0 1.0 Universal
http://www.plosone.org
http://www.plos.org
http://creativecommons.org/publicdomain/zero/1.0/ http://creativecommons.org/publicdomain/zero/1.0/
URI: http://hdl.handle.net/10315/31187
Date: 2016-04-22

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CC0 1.0 Universal Except where otherwise noted, this item's license is described as CC0 1.0 Universal