About our research
The CRC aims to elucidate structural hallmarks in various states of activation, which are linked to GPCR func-tion. A broad spectrum of methods will be applied synergistically: computational techniques, structural meth-ods, site-directed mutagenesis, crosslinking and mass spectrometry (MS), as well as functional cell-based analyses. The structural dynamics of peptide GPCRs and aGPCRs will be compared to those of the well-characterized receptors to identify common principles but also differences between receptor groups and classes. Novel aspects of signaling dynamics and protease-activated receptors will be included. Structural dynamics of GPCR activation and the modulation of receptor activation and signal selectivity, however, is the central question of all projects.
Overall, we aim to answer the following questions: How can we turn snapshots obtained by structural anal-yses in the first funding period into a consistent picture of the dynamic processes of GPCR activation and signaling? How do different types of ligands affect the dynamics and trafficking of GPCRs, and the interac-tion with different effector proteins? How is the interplay of extracellular and intracellular signaling and cou-pling mechanism orchestrated? How can we use the knowledge of the structural dynamics to obtain signaling protein profiles and to predict ligands and their activity?
The SFB1423 is divided into four major groups:
- Identification of structural snapshots of peptide and adhesion GPCRs
- GPCR activity is modulated by distinct signals that lead to stabilization of active receptor conformations, which will be studied by
- Different conformations will lead to different signaling, e.g. G protein/arrestin bias, Gi/Gs dual coupling, cis/trans-signaling
- Peptide synthesis and membrane protein (GPCR) expression & Computational models of structure, dynamics and evolution of GPCRs