Project C05 – Structural dynamics of allosteric coupling in GPCRs

Contact

Prof. Dr. Andreas Bock (Project Leader)

Leipzig University, Medical Faculty
Rudolf-Boehm-Institute of Pharmacology and Toxicology
Härtelstrasse 16-18, D-04107 Leipzig

Phone +49 341 97 24610
E-Mail

Lisa Maria Martin (PhD Student)

Max Delbrück Center for Molecular Medicine
Unit: Signaling processes of receptors
Robert-Rössle-Strasse 10, D-13125 Berlin

Pauline Löffler (PhD Student, associated)

Leipzig University, Medical Faculty
Rudolf-Boehm-Institute of Pharmacology and Toxicology
Härtelstrasse 16-18, D-04107 Leipzig

Chiara de Faveri (PhD Student)

Leipzig University, Faculty of Life Sciences
Institute of Biochemistry
Brüderstrasse 34, D-04103 Leipzig

Antonio Lopez Sierra (PhD Student)

Leipzig University, Faculty of Life Sciences
Institute of Biochemistry
Brüderstrasse 34, D-04103 Leipzig

Yasmin Aigin (PhD Student)

Leipzig University, Faculty of Life Sciences
Institute of Biochemistry
Brüderstrasse 34, D-04103 Leipzig

Resources

  • Fluorescence microscopy
  • FRET / BRET
  • High-throughput screening
  • Nucleic acid and protein assays

Publications

Bock A, Irannejad R, Scott JD. cAMP signaling: a remarkably regional affair. Trends Biochem Sci. 2024 Feb 2:S0968-0004(24)00018-5.

Aydin Y, Böttke T, Lam JH, Ernicke S, Fortmann A, Tretbar M, Zarzycka B, Gurevich VV, Katritch V*, Coin I*. Structural details of a Class B GPCR-arrestin complex revealed by genetically encoded crosslinkers in living cells. Nat Commun. 2023; 14:1151.

Lohse MJBock A, Zaccolo M. G Protein-Coupled Receptor Signaling: New Insights Define Cellular Nanodomains. Annu Rev Pharmacol Toxicol. 2023 Sep 8. doi: 10.1146/annurev-pharmtox-040623-115054. Epub ahead of print. PMID: 37683278.

Anton SE, Kayser C, Maiellaro I, Nemec K, Möller J, Koschinski A, Zaccolo M, Annibale P, Falcke M, Lohse MJ, Bock A. Receptor-associated independent cAMP nanodomains mediate spatiotemporal specificity of GPCR signaling. Cell. 2022 Mar 31;185(7):1130-1142.e11. doi: 10.1016/j.cell.2022.02.011. Epub 2022 Mar 15. PMID: 35294858.

Rudolf S, Kaempf K, Vu O, Meiler J, Beck-Sickinger AG*, Coin I*. Binding of Natural Peptide Ligands to the Neuropeptide Y5 Receptor. Angew Chem Int Ed Engl. 2022; 61:e202108738.

Bock A, Bermudez M. Allosteric coupling and biased agonism in G protein-coupled receptors. FEBS J. 2021 Feb 23. doi: 10.1111/febs.15783. Epub ahead of print. PMID: 33621418.

Işbilir A, Serfling R, Möller J, Thomas R, De Faveri C, Zabel U, Scarselli M, Beck-Sickinger AGBock ACoin ILohse MJAnnibale P. Determination of G-protein–coupled receptor oligomerization by molecular brightness analyses in single cells. Nat Protoc. 2021. https://doi.org/10.1038/s41596-020-00458-1.

Bock AAnnibale P, Konrad C, Hannawacker A, Anton SE, Maiellaro I, Zabel U, Sivaramakrishnan S, Falcke M, Lohse MJ. Optical Mapping of cAMP Signaling at the Nanometer Scale. Cell. 2020 Aug 20:S0092-8674(20)30943-0. doi: 10.1016/j.cell.2020.07.035. Epub ahead of print. PMID: 32846156.

Böttke T, Ernicke S, Serfling R, Ihling C, Burda E, Gurevich VV, Sinz A, Coin I. Exploring GPCR-arrestin interfaces with genetically encoded crosslinkers. EMBO Rep. 2020 Nov 5;21(11):e50437. doi: 10.15252/embr.202050437. Epub 2020 Sep 14. PMID: 32929862; PMCID: PMC7645262.

Holze J, Bermudez M, Pfeil EM, Kauk M, Bödefeld T, Irmen M, Matera C, Dallanoce C, De Amici M, Holzgrabe U, König GM, Tränkle C, Wolber G, Schrage R, Mohr K, Hoffmann C, Kostenis E, Bock A. Ligand-Specific Allosteric Coupling Controls G-Protein-Coupled Receptor Signaling. ACS Pharmacol Transl Sci. September 2, 2020 DOI: 10.1021/acsptsci.0c00069

Kaiser ACoin I. Capturing Peptide-GPCR Interactions and Their Dynamics. Molecules. 2020 Oct 15;25(20):4724. doi: 10.3390/molecules25204724. PMID: 33076289; PMCID: PMC7587574.

Bock A, Schrage R, Mohr K. Allosteric modulators targeting CNS muscarinic receptors. Neuropharmacology. 2018; 136:427-37.

Serfling R, Seidel L, Böttke T, Coin I. Optimizing the genetic incorporation of chemical probes into GPCRs for photo-crosslinking mapping and bioorthogonal chemistry in live mammalian cells. J Vis Exp. 2018; 134.

Serfling R, Lorenz C, Etzel M, Schicht G, Böttke T, Mörl M, Coin I. Designer tRNAs for efficient incorporation of non-canonical amino acids by the pyrrolysine system in mammalian cells. Selected as breakthrough paper, journal cover. Nucleic Acids Res. 2018; 46:1-10.

 

Bermudez M, Bock A, Krebs F, Holzgrabe U, Mohr K, Lohse MJ, Wolber G. Ligand-specific restriction of extracellular conformational dynamics constrains signaling of the M2 muscarinic receptor. ACS Chem Biol. 2017; 12:1743-8.

Seidel L, Zarzycka B, Zaidi SA, Katritch V, Coin I. Structural insight into the activation of a class B G-protein-coupled receptor by peptide hormones in live human cells. 2017; 6:27711.

Bock A, Bermudez M, Krebs F, Matera C, Chirinda B, Sydow D, Dallanoce C, Holzgrabe U, De Amici M, Lohse MJ, Wolber G, Mohr K. Ligand binding ensembles determine graded agonist efficacies at a G protein-coupled receptor. J Biol Chem. 2016; 291:16375-89.

Bock A, Chirinda B, Krebs F, Messerer R, Bätz J, Muth M, Dallanoce C, Klingenthal D, Tränkle C, Hoffmann C, De Amici M, Holzgrabe U, Kostenis E, Mohr K. Dynamic ligand binding dictates partial agonism at a G protein-coupled receptor. Nat Chem Biol. 2014; 10:18-20.

Coin I, Katritch V, Sun T, Xiang Z, Siu FY, Beyermann M, Stevens RC, Wang L. Genetically encoded chemical probes reveal the binding path of Urocortin-I to CRF Class B GPCR. 2013; 155:1258-69.

Bock A, Merten N, Schrage R, Dallanoce C, Bätz J, Klöckner J, Schmitz J, Matera C, Simon K, Kebig A, Peters L, Müller A, Schrobang-Ley J, Tränkle C, Hoffmann C, De Amici M, Holzgrabe U, Kostenis E, Mohr K. The allosteric vestibule of a seven transmembrane helical receptor controls G-protein coupling. Nat Commun. 2012; 3:1044.

Coin I, Perrin MH, Vale WW, Wang L. Photocrosslinkers incorporated into G-Protein-Coupled-Receptors in mammalian cells: a ligand comparison. Selected as Very-Important-Paper (VIP) by referees. Angew Chem Int Ed Engl. 2011; 50:8077-81.