Investigation of the thermodynamic drivers of the interaction between the high mobility group box domain of Sox2 and bacterial lipopolysaccharide

• Published in: Biochimica et biophysica acta. Biomembranes 2020-02, Vol.1862 (2), p.183106-183106, Article 183106
• Main Authors: Hewitt, Patrick H., Pianim, Ernest D., DiCesare, Nicholas A., Gray, Casey, Leong, Trung T., Sakai, Kuriko, Bernal, Jan V., Shetty, Shweta S., Malarkey, Christopher S.
• Format: Article
• Language: English
• Subjects: Gastric cancer; Helicobacter pylori - chemistry; High-mobility group box; HMG-Box Domains; Humans; Isothermal titration calorimetry; Lipopolysaccharide; Lipopolysaccharides - chemistry; Lipopolysaccharides - metabolism; Molecular Docking Simulation; Protein Binding; Sox2; SOXB1 Transcription Factors - chemistry; SOXB1 Transcription Factors - metabolism; Tryptophan fluorescence
• ISSN: 0005-2736; 1879-2642
• DOI: 10.1016/j.bbamem.2019.183106

Gastric cancer is associated with high mortality and is preceded by an infection with Helicobacter pylori (H. pylori). H. pylori stimulates inflammation which involves the activation of Toll-like receptor 4 by lipopolysaccharide molecules from the H. pylori. This leads to chronic inflammation that can eventually lead to gastric cancer. Sox2 is a member of the high mobility group (HMG) box family of proteins, and recent studies have shown that HMG box proteins can modulate immune response by altering signaling to Toll-like receptors. Sox2 is overexpressed in most types of cancer with the exception of gastric cancer where expression of Sox2 is decreased. Here, we demonstrate that Sox2 can bind LPS and we investigated the thermodynamic drivers of the Sox2/LPS interaction. [Display omitted] •Sox2 can bind lipopolysaccharide with micromolar affinity.•This is the first demonstration of a single domain high mobility group box protein binding to lipopolysaccharide molecules.•Sox2 binds lipopolysaccharide in a 2:1 ratio with endothermic and exothermic drivers of the interaction.