Short Report by Anja Wieprecht: Identification and verification of interaction partners of adhesion G protein-coupled receptors. (Aug. – Oct. 2018)

/ November 15, 2018/ Research, Students

Adhesion G protein-coupled receptors (aGPCRs) are expressed in various cell types, including cells of the immune system and central nervous system. Furthermore, they were reported to be involved in tumorgenesis. Besides their physiological relevance the majority of them have not been functionally characterized in detail. Notably, in contrast to other GPCRs this class of receptors possess an autoproteolytical site within their N-terminus at which they are cleaved. It is known that aGPCRs can be activated by their Stachel-sequence, a short tethered agonist sequence N-terminal of this cleavage site. However, both the binding pocket and the mechanism of its activation remain to be characterized. Using the smallest and noncleaved GPR114 as a proof of principle, I investigated the structural features and possible interaction sites between the Stachel-sequence and the 7-transmembrane(7TM)-region of the receptor. Importantly, aGPCRs are membranous proteins having large extracellular domains. Therefore, the experimental determination of a complete protein structure of a aGPCRS has not been possible so far. 

During the time in Jens Meilers lab I studied computational methods like Comparative Modeling and Peptide Docking by Rosetta. I had the unique opportunity to further increase my scientific knowledge regarding these methods. Here I described the first full-length model of GPR114. I intensively studied the structure and possible interaction sites based on this model. Information gained from the model will be used to design new experiments in molecular biochemistry labs, helping us to combine methods like computational work, mutagenesis and second-messenger assays to identify the amino acids that mediate the interaction between the tethered agonist and the 7TM-region.             

During my time in Nashville I experienced the traditional farmers market, lively music scene and culturally diverse restaurants. Furthermore, I had the opportunity to visit the U.S. Space and Rocket Center in Alabama.