Periodic Reporting for period 1 - proteoRAGE (Unravelling the pRotein Allosterome of Gene Expression)
Reporting period: 2021-07-01 to 2022-12-31
Proteins perform many of the chemical reactions essential to cell homeostasis, growth and proliferation. The most rapid and efficient mechanism to modulate protein activity is allosteric regulation, which depends on the direct binding between proteins and small-molecules. Since their intracellular concentration depends on environmental conditions, allosteric ligands can set responses of adaptation to the external environment independently on genetic factors. The lack of global streamlined methods to investigate allosteric mechanisms limits our current understanding of cellular physiology in health and disease. In this project we plan to elucidate how the complex network of interactions between small-molecules and proteins affects cellular responses. We will systematically measure protein structural changes produced by the binding of metabolites in the cell and which aspects of cellular activity they influence. This is important to understand the chemical reactions necessary for life and modulate them with drug molecules.
In this very first period of the project we set-up the methodological framework by showing that structural proteomics can be used to identify new drug targets in human cells.
By the end of the project we will show how environmentally-driven interactions between proteins and metabolites are driving cell fate in homeostasis and during disease.