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Graduate School of Chemical and Molecular Sciences Zurich


We are a group active in structural biology and (a bit) in protein design. We use solution nuclear magnetic resonance (NMR) as our principal technique and focus on proteins. We apply other biophysical methods to the study of proteins or protein-ligand interactions such as isothermal titration calorimetry (ITC), circular dicroism (CD), microscale thermoresis (MST) or fluorescence depolarization (FD). We usually produce the proteins by ourself, and hence we have a full equipped biochemistry lab.

The graphics below will give you an impression of the breath of our research. You will find more detailed descriptions and the relevant references on our group webpages.



Structural Characterization of Fragments from G-protein Coupled Receptors (GPCR)

G-protein coupled receptors (GPCRs) are membrane proteins that are highly dynamical and the targets of many pharmaceutical drugs. GPCRs occupy multiple conformations even in the apo state. Binding of a ligand changes the equilibrium of these states, and therefore the resulting receptor response. We use solution NMR to analyze the dynamical aspects of these conformational landscapes.


Our interests are focused on the methyl dynamics of a thermostabilized α1B adrenergic receptor. We produce perdeuterated receptor mutants that remain active in E. coli. Through solution NMR we observe the methyl groups of the isoleucine, leucine and valine side chains. With these methyl probes we aim to elucidate the molecular dynamics of the α1B adrenergic receptor.


Key references

  • M. Schuster, M. DeLuigi, M. Pantic, S. Vacca, C. Baumann, M. D. Scott, A. Plückthun and O. Zerbe: Optimizing the a1B-Adrenergic Receptor for Solution NMR Studies (2020) BBA Biomembranes, 1862, 183354.

  • L. Kooijman, P. Ansorge, M. Schuster, C. Baumann, F. Löhr, S. Jurt, P. Güntert and O. Zerbe: NMR Backbone and methyl assignment of bacteriorhodopsin incorporated into nanodiscs (2020) J. Biomol. NMR74, 45-60.

  • L. Kooijman, M. Schuster, C. Baumann, S. Jurt, F. Löhr, B. Fürtig, P. Güntert and O. Zerbe,  Dynamics of Bacteriorhodopsin in the Dark-Adapted  State from Solution NMR, Angew. Chem. Int. Ed., DOI:10.1002/anie.202004393.



Development of Novel Antibiotics

With the rise of multi-resistant bacteria, the need for novel antibiotics is increasingly urgent.  Lipopolysaccharide (LPS) is a hallmark antigen that coats the cell surface of most Gram-negative bacteria. The LPS transport (Lpt) machinery, which transports LPS across the periplasm to the outer membrane, is a novel target for a new class of antibiotics.


Thanatin, a natural antimicrobial peptide, disrupts the binding interfaces of Lpt proteins, ultimately functioning as a bactericidal agent. In collaboration with Polyphor, we are interested in the characterization of thanatin-like drug candidates using solution NMR and biophysical methods to determine their pharmacological properties.


Key references

  • S. U. Vetterli, K. Zerbe, M. Müller, M. Urfer, M. Mondal, S.-Y. Wang, K. Moehle, O. Zerbe, A. Vitale, G. Pessi, L. Eberl, B. Wollscheid and J. A. Robinson: Thanatin Targets the Inter-Membrane Protein Bridge Required for Lipopolysaccharide Transport in Escherichia coli (2018) Science Advances, 4, eaau2634.

  • K. Moehle, H. Kocherla, B. Bacsa, S. Jurt, K. Zerbe, J. A. Robinson, O.Zerbe: Solution structure and dynamics of LptE from Pseudomonas aeruginosa, Biochemistry, 55 (2016), 2936-2943.

Structure and Metal-Binding of Metallothioneins

Metallothioneins are small proteins that bind and trap heavy metal ions, which protects cells from toxic metals and helps with regulating essential ones. Most of these proteins form two domains, each being able to coordinate three or four divalent metal ions by nine or eleven cysteine residues.


Metallothioneins in snails show a large diversity in primary structures. Some of these metallothioneins became metal selective, which allowed snails to adapt to different environments. The benefits of other modifications such as domain multiplications are not yet understood. We use solution NMR to shed light on the evolution of these proteins, focusing on metal uptake, transfer and selectivity of snail metallothioneins.


Key References

  • C. Baumann, A. Beil. S. Jurt, M Niederwanger, O. Palacios, M. Capdevila, S. Atrian, R. Dallinger, O. Zerbe: Structural adaptation of a protein to increased metal stress: NMR structure of a marine snail metallothionein with an additional domain (2017) Angew. Chem.Int. Ed., 56, 4617-4622.

  • A. Beil, S. Jurt, R. Walser, T. Schönhut, P. Güntert, Òscar Palacios, S. Atrian, Mercè Capdevila, R. Dallinger, O. Zerbe: The Solution Structure and Dynamics of Cd-Metallothionein from Helix pomatia Reveal Optimization for Binding Cd over Zn. (2019) Biochemistry58, 470-4581.

  • R. Dallinger, O. Zerbe, C. Baumann, B. Egger, M. Capdevila, O. Palacios, R. Albalat, S. Calatayud, P. Ladurner, B. Schlick-Steiner, F. Steiner, V. Pedrini-Martha, R. Lackner, H. H. Lindner, M. Dvorak, M. Niederwanger, R. Schnegg and S. Atrian: Variable environmental cadmium levels through the last 445 million years have triggered convergent evolution of Cd-selective snail metallothioneins and their metal-specific diversification (2020) Metallomics, 12, 702.

Repeat Proteins

Armadillo repeat proteins are artificially designed proteins developed in the group of Andreas Plückthun. Armadillo repeat proteins (nArmRP), are characterized by an Armadillo domain, composed by several tandem Armadillo repeats each comrpising 42 amino acid residues. These repeats can mediate interactions to a peptide or a part of protein in an extended conformation. Therein, each Armadillo repeat is able to bind a single specific dipeptide.

The specificity is given by the primary sequence of the repeat: changing the sequence will change the dipeptide target. Interestingly, the individual modules can be arranged in arbitrary order, and hence having access to modules with specific binding capabilities will allow constructing peptide binders from scratch (in silico). Accordingly, these modular-peptide binders could represent a cheap and fast alternative to the more expensive and laborious monoclonal antibodies.

In our group, we investigate the protein-peptide interaction by solution NMR. We determine overall structural features of the designed ArmRPs such as the curvature of the protein (and in particular changes to curvature due to peptide binding) by probing the complex with specifically designed chemical tags, we develop new techniques in isotope labelling to overcome assignment challenges, and exploit the structure modularity to assemble new supramolecular structures.


Key references

  • E. Michel, A. Plückthun, O. Zerbe: Peptide binding affinity redistributes preassembled repeat protein fragments (2019) Biol. Chem.400, 393-404.

  • E. Michel, A. Plückthun, O. Zerbe: Peptide-Guided Assembly of Repeat Protein Fragments (2018) Angew. Chem. Int. Ed.57, 4576-4579.

  • C. Ewald, M.T. Christen, R. Watson, M. Mihajlovic, T. Zhou, A. Honegger, A. Plückthun, A. Caflisch, O. Zerbe: A Combined NMR and Computational Approach to Investigate Peptide Binding to a Designed Armadillo Repeat Protein (2015) J. Mol. Biol.427,1916-1933.

  • R. Watson, M. Christen, C. Ewald, F. Bumback, C. Reichen, M. Mihajlovic, E. Schmidt, P. Güntert, A. Plückthun, A. Caflisch, O. Zerbe (2014): Spontaneous Self-Assembly of Engineered Armadillo Repeat Protein Fragments into a Folded Structure, Structure22, 985-995.