Renoprotection by understanding functional and structural G-protein-coupled receptor activation (A03)

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Autoantibodies (immunoglobulins - IgGs) induce several renal pathologies by targeting the G-protein-coupled receptors (GPCRs), Angiotensin II type 1 and Endothelin-1 type A. We aim to identify and characterize determinants and signaling pathways that are specific for pathogenic IgG binding and receptor-activation as compared to endogenous peptide receptor-agonists. By a combination of G-protein signaling assays in yeast or mammalian cells with biophysical in vitro assays, protein X-ray crystallography and cryo-electron microscopy, we will elucidate molecular insights into autoimmune GPCR activation, which finally will support a rational design of new specific renoprotective drugs.