Structural elucidation of the GPCR allosteric machine (B06)

• Subject Area: Biophysics
• Term: from 2011 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 25065445

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 ß2-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 Ga subunit (GaCT) 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 GaCT and ArrFL, enabling modelling, MD simulations and protein X-ray crystallography of complexes of R* with Gi or arrestin.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 740: From Molecules to Modules: Organisation and Dynamics of Functional Units in Cells
• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Project Heads: Professor Dr. Peter Hildebrand; Dr. Patrick Scheerer, since 1/2015