Title:Structural Basis of Human Transcription Factor Sry-related Box 17 Binding to DNA
Volume: 20
Issue: 4
Author(s): Nana Gao, Wei Jiang, Hai Gao, Zhong Cheng, Huolian Qian, Shuyi Si and Yong Xie
Affiliation:
Keywords:
Transcription factor, Sry-related box 17 (Sox17), HMG-domain, Crystal Structure, DNA-binding, groove, cell lineage, molecular mechanism, protein, organogenesis
Abstract: Sry-related box (Sox) transcription factors share a conserved high-mobility-group box domain (HMG-domain)
that binds DNA in the minor groove and bends DNA for further assembly of transcriptional machineries. During organogenesis,
each member of the Sox family triggers a specific cell lineage differentiation, indicating that their interactions
with DNA are different from each other. Therefore, investigating structural rearrangement of each Sox transcription factor
HMG-domain upon binding to DNA would help to elucidate the distinctive molecular mechanism by which they interact
with DNA. Previous studies have determined the crystal structures of Sox2 HMG-domain/DNA, Sox4 HMGdomain/
DNA, Sox9 HMG-domain/DNA and Sox17 HMG-domain/DNA complexes. However, major gaps remain in the
structural information on the Sox transcription factor HMG-domains. Here, we report the crystal structure of the human
Sox17 HMG-domain alone at 2.4 A resolution. Comparing this structure and the structure of the mouse Sox17 HMGdomain/
DNA complex provides structural understanding of the mechanism of Sox17 binding to DNA. Specifically, after
electrostatic interactions attract Sox17 to DNA, Asn73, Ser99, and Trp106 form hydrogen bonds with DNA, Arg70,
Lys80, Arg83, His94, and Asn95 on Sox17 undergo conformational changes and form hydrogen bonds with DNA, contributing
to the electrostatic interaction between Sox17 and DNA.
