Abstract 1141 S100A12 thermodynamic stability and misfolding properties: Assessing the capacity of S100A12 to misfold into amyloid-like structures

S100A12 is a protein implicated in chronic inflammation, an innate characteristic in cancer and many other diseases. S100A12 is a small calcium binding protein that activates the receptor for advanced glycation end product (RAGE) which stimulates production of pro inflammatory molecules. Understanding the biochemical pathway that contributes to chronic inflammation is key to inform future therapeutic treatments. Here, we report that S100A12 leads to increased inflammation in a H. pylori infected mouse, an animal model for stomach cancer. Additionally, S100A12 aggregates into amyloid structure in gastric tissue. We used electron microscopy to demonstrate that recombinantly expressed S100A12 is able to form amyloid structures via an acid mediated misfolding pathway. Differential scanning fluorimetry experiments suggest low pH destabilizes the S100A12 native structure and results in a reduced melting temperature. In total, these preliminary data provide a rationale for studying the misfolding/unfolding properties of S100A12 and may provide insights into molecular mechanisms associated with chronic inflammation. I would like to thank all staff in the Damo lab and the Fisk-Vanderbilt bridge program for the support and mentorship through my research progress . This research is funded by CZI 2022-253614, NSF EES2112556, NSF EES1764201, NSF MCB1955975, and NIH GM105551.