Calcium domain in Orai1 regulates NFAT dependent genes

This project examines a novel Ca2+ binding domain at the pore entrance of the Ca2+ channel Orai1. This important Ca2+ channel, triggering T cell activation and mast cells degranulation, contains a unique pore structure different to the pore-loop architecture of many other ion-selective channels. A combination of functional live cell experiments with molecular dynamics simulations will reveal the interplay of the extracellular calcium binding domain and the nearby selectivity filter. Particularly, we will investigate how the channel adjusts to environmental Ca2+ and maintains Ca2+ permeation in ubiquitous cell types. Furthermore, we will determine how Orai1 mediated Ca2+ micro-domains activate transcription factors, including the Nuclear Factor of Activated T-cells (NFAT).