Structural studies on extracellular adhesion GPCR signaling
Mehmet Volkan Cakir
Adhesion-G-Protein-coupled Receptors (aGPCR) are a large receptor family which has been only partially investigated so far concerning its biochemical, structural and functional properties. The aim of the project is to characterise the spatial structures of the receptors and their interactions with binding partners by X-ray structure analysis. Such studies are the basis to understand the molecular function of the receptors and for a structure-based development of potential drugs acting on these receptors. To this end, the receptors and single domains are expressed in three different expression systems: E. coli, HEK cells and insect cells. For structural and biophysical investigations milligram quantities of highly pure protein need to be prepared. The following processes in the mode of action of the receptors will be primarily studied: The binding of ligands to the extracellular binding domains and the conformational changes in the interaction of the binding domains and the GAIN domains induced thereby and, furthermore, the interaction between the GAIN domain and the transmembrane part, which is probably conserved in all aGPCR.
Röthe J, Thor D, Winkler J, Knierim A, Binder C, Huth S, Kraft R, Rothemund S, Schöneberg T, Prömel S (2019) Involvement of the Adhesion GPCRs Latrophilins in the Regulation of Insulin Release. Cell Reports. 26: 1573–1584.