Project B05 – Structural consequences of adhesion GPCR activation

This project aims to elucidate how mechanical force, extracellular interaction partners and the tethered agonist interplay in a concerted sequence to induce the active state of adhesion GPCRs. We will fill the gap between available functional and structural data by adding new structural information using basic biochemical approaches (cross linking, Western Blot, ELISA), Fluorescence Resonance Energy Transfer (FRET) techniques and electron paramagnetic resonance (EPR). We will identify and compare different forms of mechanical forces that are sufficient for aGPCR activation and we will study the structural changes of the N terminus, the Stachel sequence and the 7TM upon peptide and mechanical force application.

Contact

Prof. Dr. Ines Liebscher (Project Leader)

Leipzig University, Faculty of Medicine
Rudolf Schönheimer Institute of Biochemistry
Johannisallee 30, D-04103 Leipzig

Phone +49 341 97 22175
E-Mail
Web /research/ag_liebscher

Dr. Caroline Wilde (Senior Scientist)

Leipzig University, Faculty of Medicine
Rudolf Schönheimer Institute of Biochemistry
Johannisallee 30, D-04103 Leipzig

Phone +49 341 97 22176
E-Mail

Resources

  • Cross Linking, Western Blot & ELISA
  • Fluorescence Resonance Energy Transfer (FRET) techniques and 
  • electron paramagnetic resonance (EPR)

Publications

Coming soon.

Mogha A, Benesh AE, Patra C, Engel FB, Schöneberg T, Liebscher I, Monk KR. Gpr126 functions in Schwann cells to control differentiation and myelination via G-protein activation. J Neurosci. 2013; 33:17976-85.

Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, Hall RA, Harty BL, Kirchhoff C, Knapp B, Krishnan A, Liebscher I, Lin HH, Martinelli DC, Monk KR, Peeters MC, Piao X, Prömel S, Schöneberg T, Schwartz TW, Singer K, Stacey M, Ushkaryov YA, Vallon M, Wolfrum U, Wright MW, Xu L, Langenhan T, Schiöth HB. International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors. Pharmacol Rev. 2015; 67:338-67.

Liebscher I*, Schön J*, Petersen SC, Fischer L, Auerbach N, Demberg LM, Mogha A, Cöster M, Simon KU, Rothemund S,Monk KR, Schöneberg T. A tethered agonist within the ectodomain activates the adhesion G protein-coupled receptors GPR126 and GPR133. Cell Rep. 2014; 9:2018-26.

Demberg LM, Rothemund S, Schöneberg T, Liebscher I. Identification of the tethered peptide agonist of the adhesion G protein-coupled receptor GPR64/ADGRG2. 2015; 464:743-7.

Wilde C, Fischer L, Lede V, Kirchberger J, Rothemund S, Schöneberg T, Liebscher I. The constitutive activity of the adhesion GPCR GPR114/ADGRG5 is mediated by its tethered agonist. FASEB J. 2016; 30:666-73.

Demberg LM, Winkler J, Wilde C, Simon KU, Schön J, Rothemund S, Schöneberg T, Prömel S*, Liebscher I*. Activation of adhesion G protein-coupled receptors: agonist specificity of Stachel sequence-derived peptides. J Biol Chem. 2017; 292:4383-94.

Hsiao CC, Chu TY, Wu CJ, van den Biggelaar M, Pabst C, Hébert J, Kuijpers TW, Scicluna BP, I KY, Chen TC, Liebscher I, Hamann J, Lin HH. The adhesion G protein-coupled receptor GPR97/ADGRG3 is expressed in human granulocytes and triggers antimicrobial effector functions. Front Immunol. 2018; 9:2830.

Hilbig D, Sittig D, Hoffmann F, Rothemund S, Warmt E, Quaas M, Stürmer J, Seiler L, Liebscher I, Hoang NA, Käs JA, Banks L, Aust G. Mechano-Dependent Phosphorylation of the PDZ-Binding Motif of CD97/ADGRE5 Modulates Cellular Detachment. Cell Rep. 2018; 24:1986-95.

Petersen SC*, Luo R*, Liebscher I*, Giera S, Jeong SJ, Mogha A, Ghidinelli M, Feltri ML, Schöneberg T, Piao X, Monk KR. The adhesion GPCR GPR126 has distinct, domain-dependent functions in Schwann cell development mediated by interaction with laminin-211. Neuron. 2015; 85:755-69.

Monk KR, Hamann J, Langenhan T, Nijmeijer S, Schöneberg T, Liebscher I. Adhesion G Protein-Coupled Receptors: From In vitro Pharmacology to In vivo Mol Pharmacol. 2015; 88:617-23.