WPE_6899_460x337.jpg

B6 Prof. Dr. Peter Hildebrand / Prof. Dr. Patrick Scheerer

You are here:

B6: Structural elucidation of the GPCR allosteric machine

We apply complementary in silico and in vitro structural biology methods to obtain insights into the dynamic modulation of G protein coupled receptors by ligands or signal transducers. To address the key question of G protein coupling specificity we investigate the role of the open cytoplasmic crevice of the human β2-adrenoceptor or bovine rhodopsin in selective binding of Gi, Gs or arrestins. We use native and mutant peptides derived from the key binding sites of the Gα subunit (GαCT) or arrestin (finger loop, ArrFL) to elucidate their role in the selective (on/off) switching of downstream signaling pathways. Our long term goal is to obtain high affinity variants of GαCT and ArrFL, enabling modelling, MD simulations and protein X-ray crystallography of complexes of R* with Gi or arrestin.

Selected Publications