Talk given by Isabella Derler (University Linz, Austria) as part of the International GCE Webinar series. Live talk given on February 15th, 2024.
The Orai1 Ca2+ ion channel is a main route for Ca2+ ions to enter the cell and essential to maintain a variety of human body functions such as immune response. To resolve individual TM domain motions crucial for Orai1 pore opening, we employed photocrosslinking unnatural amino acids (UAAs). We demonstrated that the incorporation of a photocrosslinking UAA into one of the Orai1 TM domains is suitable to transfer light-sensitivity to the channel complex, activate physiological Orai1 currents and trigger downstream signaling. We expect to use this technology to resolve individual TM domain motions critical for pore opening, which may serve as a fundament for future drug developments.