Project B01 – Molecular mechanisms of allosteric modulators at Y-receptors


Prof. Dr. Annette Beck-Sickinger (Project Leader)

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

Phone +49 341 97 36 900

Corinna Schüss (Post Doc)

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

Lisa Peuker (PhD Student)

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

Hannah Lentschat (PhD Student)

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

Tim Pelczyk (PhD Student)

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

Manuel Troll (PhD Student, associated)

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


Unit Center Mass Spectrometry (>> Link)

  • Bruker Daltonics Microflex MALDI-ToF Massenspektrometer
  • Bruker Daltonics Ultraflex III MALDI-ToF/ToF
  • Bruker Daltonics Esquire HCT
  • Thermo Scientific Orbitrap Elite


Schüß C, Behr V, Beck-Sickinger AG. Illuminating the neuropeptide Y4 receptor and its ligand pancreatic polypeptide from a structural, functional, and therapeutic perspective. Neuropeptides. 2024 Feb 24;105:102416. doi: 10.1016/j.npep.2024.102416 .

Schüß C, Vu O, Mishra NM, Tough IR, Du Y, Stichel J, Cox HM, Weaver CD, Meiler J, Emmitte KA, Beck-Sickinger AG. Structure-Activity Relationship Study of the High-Affinity Neuropeptide Y4 Receptor Positive Allosteric Modulator VU0506013. J Med Chem. 2023 Jul 13;66(13):8745-8766.

Zhang X, Weiß T, Cheng MH, Chen S, Ambrosius CK, Czerniak AS, Li K, Feng M, Bahar I, Beck-Sickinger AG, Zhang C. Structural basis of G protein-Coupled receptor CMKLR1 activation and signaling induced by a chemerin-derived agonist. PLoS Biol. 2023 Dec 6;21(12):e3002188.

Rudolf S, Kaempf K, Vu O, Meiler J, Beck-Sickinger AGCoin I. Binding of Natural Peptide Ligands to the Neuropeptide Y5 Receptor. Angew Chem Int Ed Engl. 2022 Jan 26;61(5):e202108738. doi: 10.1002/anie.202108738 . PMID:34822209. 

Tang T, Tan Q, Han S, Diemar A, Löbner K, Wang H, Schüß C, Behr V, Mörl K, Wang M, Chu X, Yi C, Keller M, Kofoed J, Reedtz-Runge S, Kaiser ABeck-Sickinger AG, Zhao Q, Wu B. Receptor-specific recognition of NPY peptides revealed by structures of NPY receptors. Sci Adv. 2022 May 6;8(18):eabm1232. doi: 10.1126/sciadv.abm1232. Epub 2022 May 4. PMID: 35507650; PMCID: PMC9067930.

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.

Tang T, Hartig C, Chen Q, Zhao W, Kaiser A, Zhang X, Zhang H, Qu H, Yi C, Ma L, Han S, Zhao Q, Beck-Sickinger AG, Wu B. Structural basis for ligand recognition of the neuropeptide Y Y2 receptor. Nat Commun. 2021 Feb 2;12(1):737. doi: 10.1038/s41467-021-21030-9. PMID: 33531491; PMCID: PMC7854658.

Schüß C, Vu O, Schubert M, Du Y, Mishra NM, Tough IR, Stichel J, Weaver CD, Emmitte KA, Cox HM, Meiler J, Beck-Sickinger AG. Highly selective Y4 receptor antagonist binds in an allosteric binding pocket. J Med Chem. 2021; 64:2801-2814.

Wanka L, Behr V, Beck-Sickinger AG. Arrestin-dependent internalization of rhodopsin-like G protein-coupled receptors. Biol Chem. 2021 May 26. doi: 10.1515/hsz-2021-0128. Epub ahead of print. PMID: 34036761.

Wolf P, Mohr A, Gavins G, Behr V, Mörl K, Seitz O, Beck-Sickinger AG. Orthogonal Peptide-Templated Labeling Elucidates Lateral ETA R/ETB R Proximity and Reveals Altered Downstream Signaling. Chembiochem. 2021 Oct 26. doi: 10.1002/cbic.202100340 . Epub ahead of print. PMID: 34699123.

Ziffert I, Kaiser A, Hoppenz P, Mörl K, Beck-Sickinger AG. Shuttling of peptide-drug conjugates by G protein-coupled receptors is significantly improved by pulsed application. ChemMedChem. 2021; 16:164-178.

Kaiser A, Wanka L, Ziffert I, Beck-Sickinger AG. Biased agonists at the human Y(1) receptor lead to prolonged membrane residency and extended receptor G protein interaction. Cell Mol Life Sci. 2020; 77:4675-4691.

Ziffert I, Kaiser A, Babilon S, Mörl K, Beck-Sickinger AG. Unusually persistent Gαi-signaling of the neuropeptide Y2 receptor depletes cellular Gi/o pools and leads to a Gi-refractory state. Cell Commun Signal. 2020; 18:49.

Kögler LM, Stichel J, Kaiser A, Beck-Sickinger AG. Cell-Free Expression and Photo-Crosslinking of the Human Neuropeptide Y2 Receptor. Front Pharmacol. 2019; 10:176.

Yang Z*, Han S*, Keller M*, Kaiser A*, Bender BJ*, Bosse M, Burkert K, Kögler LM, Wifling D, Bernhardt G, Plank N, Littmann T, Schmidt P, Yi C, Li B, Ye S, Zhang R, Xu B, Larhammar D, Stevens RC, Huster D, Meiler J, Zhao Q, Beck-Sickinger AG#, Buschauer A, Wu B#. Structural basis of ligand binding modes of neuropeptide Y Y1. Nature. 2018; 556:520-4.

Kaiser A, Hempel C, Wanka L, Schubert M, Hamm HE, Beck-Sickinger AG. G Protein Preassembly Rescues Efficacy of W(6.48) Toggle Mutations in Neuropeptide Y(2) Receptor. Mol Pharmacol. 2018; 93:387-401.

Wanka L, Babilon S, Kaiser A, Mörl K, Beck-Sickinger AG. Different mode of arrestin-3 binding at the human Y(1) and Y(2) receptor. Cell Signal. 2018; 50:58-71.

Schubert M, Stichel J, Du Y, Tough IR, Sliwoski G, Meiler J, Cox HM, Weaver CD, Beck-Sickinger AG. Identification and Characterization of the First Selective Y(4) Receptor Positive Allosteric Modulator. J Med Chem. 2017; 60:7605-12.

Burkert K*, Zellmann T*, Meier R, Kaiser A, Stichel J, Meiler J, Mittapalli GK, Roberts E, Beck-Sickinger AG. A Deep Hydrophobic Binding Cavity is the Main Interaction for Different Y(2) R Antagonists. ChemMedChem. 2017; 12:75-85.

Wanka L, Babilon S, Burkert K, Mörl K, Gurevich VV, Beck-Sickinger AG. C-Terminal motif of human neuropeptide Y(4) receptor determines internalization and arrestin recruitment. Cell Signal. 2017; 29:233-9.

Thieme V, Jolly N, Madsen AN, Bellmann-Sickert K, Schwartz TW, Holst B, Cox HM, Beck-Sickinger AG. High molecular weight PEGylation of human pancreatic polypeptide at position 22 improves stability and reduces food intake in mice. Br J Pharmacol. 2016; 173:3208-21.

Sliwoski G*, Schubert M*, Stichel J, Weaver D, Beck-Sickinger AG, Meiler J. Discovery of Small-Molecule Modulators of the Human Y4. PLoS One. 2016; 11:e0157146.

Mäde V, Babilon S, Jolly N, Wanka L, Bellmann-Sickert K, Diaz Gimenez LE, Mörl K, Cox HM, Gurevich VV, Beck-Sickinger AG. Peptide modifications differentially alter G protein-coupled receptor internalization and signaling bias. Angew Chem Int Ed Engl. 2014; 53:10067.

Pedragosa-Badia X, Sliwoski GR, Dong Nguyen E, Lindner D, Stichel J, Kaufmann KW, Meiler J, Beck-Sickinger AG. Pancreatic polypeptide is recognized by two hydrophobic domains of the human Y4 receptor binding pocket. J Biol Chem. 2014; 289:5846-59.