Structures of adhesion GPCR by cryo-electron microscopy (A05)

• Subject Area: Biochemistry ; Pharmacology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 421152132

Several 3D-structures of adhesion GPCRs (aGPCRs) have been solved, but this information is still limited to a few receptor examples, partial structures and mostly active conformations of the transmembrane domain (TMD). An important open question is the interplay between the TMD and the N terminus. The N terminus, with up to 6.000 amino acids, is predisposed to integrate a variety of signals such as ligand binding, cell-cell (matrix) contacts and even mechanical forces into intracellular signals. Various important general and detailed steps in this signaling process are not yet understood, partly due to a lack of structural information. Therefore, project A05 aims to study the 3D-structures of different full-length aGPCRs and aGPCR complexes, either in (in-)active or basal conformation, using single-particle cryo-electron microscopy and cryo-electron tomography.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1423: Structural Dynamics of GPCR Activation and Signaling
• Applicant Institution: Universität Leipzig
• Project Heads: Dr. Patrick Scheerer; Professor Dr. Torsten Schöneberg; Professor Dr. Christian M. T. Spahn