Prof. Dr. Gebhard Schertler

Division Head of Biology and Chemistry

Paul Scherrer Institute
Forschungsstrasse 111
5232 Villigen PSI
Switzerland
Telephone
+41 56 310 42 65

Secretariat

Francine Weber

Curriculum Vitae

Class A G protein-coupled receptor (GPCRs) transduce extracellular signals across the cell membrane by activating cytoplasmic-bound heterotrimeric GTP binding proteins (G proteins), which, in turn, modulate the activity of downstream effector proteins. Despite the physiological and pharmacological relevance of GPCRs, the structural basis of ligand efficacy and receptor activation, and how these elements translate into cytoplasmic trafficking and cellular response still remain elusive. In the Laboratory for Biomolecular Research we integrate data from structural biology, molecular biology, cellular biology and structural bioinformatics to study the molecular basis of GPCR function. Specifically, we aim to obtain the crystal structure of the complexes between GPCRs and their cytoplasmic partners, the centerpieces that connect extracellular stimuli to intracellular signals. In addition, we plan to compare the profile of activated signaling molecules with their dynamic intracellular localization pattern to learn how receptor activation translates into specific pathways of cellular signaling. Combination of the data resulting from the study of different Class A GPCRs will allow us to obtain a global picture of GPCR signaling. Our goal is to link receptor structure, cellular biological data and pharmacological results to physiological function.

Isogai S, Deupi X, Opitz C, Heydenreich FM, Tsai CJ, Brueckner F, Schertler GF, Veprintsev DB, Grzesiek S.
Nature.2016;530(7589):237-41.

Molecular signatures of G-protein-coupled receptors(link is external)
Venkatakrishnan AJ, Deupi X, Lebon G, Tate CG, Schertler GF, Babu MM.
Nature2013;494(7436):185-94

The structural basis for agonist and partial agonist action on a β(1)-adrenergic receptor.(link is external)
Warne T, Moukhametzianov R, Baker JG, Nehmé R, Edwards PC, Leslie AG, Schertler GF, Tate CG.
Nature.2011;469(7329):241-4.

The structural basis of agonist-induced activation in constitutively active rhodopsin.(link is external)
Standfuss J, Edwards PC, D'Antona A, Fransen M, Xie G, Oprian DD, Schertler GF.
Nature.2011;471(7340):656-60.
  • Haider RS, Wilhelm F, Rizk A, Mutt E, Deupi X, Peterhans C, et al.
    Arrestin-1 engineering facilitates complex stabilization with native rhodopsin
    Scientific Reports. 2019; 9(1): 439. https://doi.org/10.1038/s41598-018-36881-4
    DORA PSI
  • Mayer D, Damberger FF, Samarasimhareddy M, Feldmueller M, Vuckovic Z, Flock T, et al.
    Distinct G protein-coupled receptor phosphorylation motifs modulate arrestin affinity and activation and global conformation
    Nature Communications. 2019; 10: 1261 (14 pp.). https://doi.org/10.1038/s41467-019-09204-y
    DORA PSI
  • Nagata T, Koyanagi M, Tsukamoto H, Mutt E, Schertler GFX, Deupi X, et al.
    The counterion–retinylidene Schiff base interaction of an invertebrate rhodopsin rearranges upon light activation
    Communications Biology. 2019; 2: 180 (9). https://doi.org/10.1038/s42003-019-0409-3
    DORA PSI
  • Tsai C-J, Marino J, Adaixo R, Pamula F, Mühle J, Maeda S, et al.
    Cryo-EM structure of the rhodopsin-Gαi-βγ complex reveals binding of the rhodopsin C-terminal tail to the Gβ subunit
    eLife. 2019. https://doi.org/10.7554/eLife.46041
    DORA PSI
  • Varma N, Mutt E, Mühle J, Panneels V, Terakita A, Deupi X, et al.
    Crystal structure of jumping spider rhodopsin-1 as a light sensitive GPCR
    Proceedings of the National Academy of Sciences of the United States of America PNAS. 2019. https://doi.org/10.1073/pnas.1902192116
    DORA PSI
  • Gerrard E, Mutt E, Nagata T, Koyanagi M, Flock T, Lesca E, et al.
    Convergent evolution of tertiary structure in rhodopsin visual proteins from vertebrates and box jellyfish
    Proceedings of the National Academy of Sciences of the United States of America PNAS. 2018; 115(24): 6201-6206. https://doi.org/10.1073/pnas.1721333115
    DORA PSI
  • Koehl A, Hu H, Maeda S, Zhang Y, Qu Q, Paggi JM, et al.
    Structure of the μ–opioid receptor–Gi protein complex
    Nature. 2018; 558(7711): 547-552. https://doi.org/10.1038/s41586-018-0219-7
    DORA PSI
  • Lesca E, Panneels V, Schertler GFX
    The role of water molecules in phototransduction of retinal proteins and G protein-coupled receptors
    Faraday Discussions. 2018; 207: 27-37. https://doi.org/10.1039/c7fd00207f
    DORA PSI
  • Maeda S, Koehl A, Matile H, Hu H, Hilger D, Schertler GFX, et al.
    Development of an antibody fragment that stabilizes GPCR/G-protein complexes
    Nature Communications. 2018; 9(1): 3712. https://doi.org/10.1038/s41467-018-06002-w
    DORA PSI
  • Mattle D, Kuhn B, Aebi J, Bedoucha M, Kekilli D, Grozinger N, et al.
    Ligand channel in pharmacologically stabilized rhodopsin
    Proceedings of the National Academy of Sciences of the United States of America PNAS. 2018; 115(14): 3640-3645. https://doi.org/10.1073/pnas.1718084115
    DORA PSI
  • Nogly P, Weinert T, James D, Carbajo S, Ozerov D, Furrer A, et al.
    Retinal isomerization in bacteriorhodopsin captured by a femtosecond x-ray laser
    Science. 2018; 361(6398): eaat0094. https://doi.org/10.1126/science.aat0094
    DORA PSI
  • Tsai C-J, Pamula F, Nehmé R, Mühle J, Weinert T, Flock T, et al.
    Crystal structure of rhodopsin in complex with a mini-Go sheds light on the principles of G protein selectivity
    Science Advances. 2018; 4(9): aat7052. https://doi.org/10.1126/sciadv.aat7052
    DORA PSI
  • Abela R, Beaud P, van Bokhoven JA, Chergui M, Feurer T, Haase J, et al.
    Perspective: Opportunities for ultrafast science at SwissFEL
    Structural Dynamics. 2017; 4(6): 61602. https://doi.org/10.1063/1.4997222
    DORA PSI
  • Haider RS, Rizk A, Schertler GFX, Ostermaier MK
    Comprehensive analysis of the role of arrestin residues in receptor binding
    In: Gurevich VV, ed. The structural basis of arrestin functions. Cham: Springer; 2017. https://doi.org/10.1007/978-3-319-57553-7_7
    DORA PSI
  • Weinert T, Olieric N, Cheng R, Brünle S, James D, Ozerov D, et al.
    Serial millisecond crystallography for routine room-temperature structure determination at synchrotrons
    Nature Communications. 2017; 8(1): 542 (11 pp.). https://doi.org/10.1038/s41467-017-00630-4
    DORA PSI
  • Standfuss J, Edwards PC, D'Antona A, Fransen M, Xie G, Oprian DD, et al.
    The structural basis of agonist-induced activation in constitutively active rhodopsin
    Nature. 2011; 471(7340): 656-660. https://doi.org/10.1038/nature09795
    DORA PSI