Project 04

Structural studies on extracellular adhesion GPCR signaling

Norbert Sträter & Torsten Schöneberg, Leipzig University

Team members
Björn Kieslich
Mehmet Volkan Cakir

Project Description
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.

Publications

Suchý T, Zieschang C, Popkova Y, Kaczmarek I, Weiner J, Liebing AD, Çakir MV, Landgraf K, Gericke M, Pospisilik JA, Körner A, Heiker JT, Dannenberger D, Schiller J, Schöneberg T, Liebscher I, Thor D (2020) The repertoire of Adhesion G protein-coupled receptors in adipocytes and their functional relevance. Int J Obes (Lond). doi: 10.1038/s41366-020-0570-2. [Epub ahead of print]. 

Knierim AB, Röthe J, Çakir MV, Lede V, Wilde C, Liebscher I, Thor D, Schöneberg T. Genetic basis of functional variability in adhesion G protein-coupled receptors. Sci Rep. 2019; 9:11036. 

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. 

Scholz N, Langenhan T, Schöneberg T (2019) Revisiting the classification of adhesion GPCRs. Annals of the New York Academy of Sciences. doi: 10.1111/nyas.14192. [Epub ahead of print] 

Schöneberg T, Prömel S (2019) Latrophilins and Teneurins in Invertebrates: No Love for Each Other? Front. Neurosci.