Structural basis of human transcription factor Sry-related box 17 binding to DNA.
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.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical college, Tian Tan Xi Li, Beijing 100050, People’s Republic of China.
Nana
N
Gao
Wei
W
Jiang
Hai
H
Gao
Zhong
Z
Cheng
Huolian
H
Qian
Shuyi
S
Si
Yong
Y
Xie
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D024742:HMG-Box Domains; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D055760:SOXF Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
C109188:SOX17 protein, human; D055760:SOXF Transcription Factors; D004247:DNA