Psoriasin (S100A7) is associated with numerous diseases, including psoriasis, cancer, and Alzheimer’s disease. S100A7 is one of 20 members belonging to the S100 family of proteins, and is a ligand of the receptor for advanced glycation endproducts (RAGE). Interestingly, the S100 family protein koebnerisin (S100A15) only differs in eight amino acids from S100A7, but does not bind to RAGE. The S100A7 residues important for binding to its receptor are still unknown. Here, we determine whether targeted mutations within S100A7 will inhibit binding to RAGE. We created point mutants of S100A7 and expressed them in cancer cells to test which region of S100A7 is imperative for binding. We performed a western blot analysis to test the expression and secretion of S100A7, S100A7 mutants, and S100A15. Then, we analyzed binding of the proteins to RAGE using co-immunoprecipitation. Our findings could help the development of a comprehensive mutation–binding analysis of S100A7 and other S100 family members with RAGE, and aid in the development of an inhibitor of S100A7-RAGE binding.
PROJECT: Identifying key residues of S100A7 important for receptor binding
The Broad has taught me that diversity within science includes bringing mathematicians, computer scientists, and biochemists together to solve biomedical issues that affect millions around the world. Through collaboration, science is able to move forward to innovation. SRPG has cultivated my professional development as a scientist, and my lab has encouraged me to ask the tough questions about disease. Also, I have learned from the faculty to be open to new opportunities throughout my career. It’s never too late to learn a new field, programming language, or set of experiments; you just need will and determination. To be comfortable with being uncomfortable is a new personal goal of mine.