Cells communicate with each other and with their environment via receptors. The G protein-coupled receptors (GPCRs) are the largest group of membrane receptors and occur in almost all living organisms. In the Collaborative Research Centre 1423 „Structural Dynamics of GPCR Activation and Signaling„, scientists from the life sciences, medicine, pharmacy and bioinformatics of our university are investigating the interactions of GPCRs, the peptide receptors and the adhesion receptors, which have so far been little studied, together with their partners at the Charité – Universitätsmedizin Berlin, the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Martin Luther University Halle-Wittenberg.
The aim of this CRC initiative is to understand the structural dynamics of ligand binding, signal transduction, and downstream control of G protein- and arrestin-signaling pathways using native ligands as well as artificial probe molecules in conjunction with hybrid methods of structural biology including NMR, X-ray (conventional and serial protein X-ray crystallography at synchrotrons and free electron lasers), cryo-electron microscopy, mass spectrometry and computational methods (molecular modeling and dynamics). Phenomena such as biased signaling are tackled using assays that target specific signaling pathways. Results are tied in with a phylogenetic analysis of GPCRs, arrestins and G proteins. One goal of the CRC is to clarify the dynamic structural states of these GPCRs in order to understand their functions. This could lead to the development of novel therapeutics for this class of GPCRs.