Research by Gebhard Schertler

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.

Representative publications

Molecular signatures of G protein-coupled receptors.
Venkatakrishnan AJ, Deupi X, Lebon G, Tate CG, Schertler GF, Babu MM.
Nature. 2013;494(7436):185-94.

The structural basis for agonist and partial agonist action on a β(1)-adrenergic receptor.
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.
Standfuss J, Edwards PC, D'Antona A, Fransen M, Xie G, Oprian DD, Schertler GF.
Nature. 2011;471(7340):656-60.
Prof. Gebhard F.X. Schertler
Department Head of Biology and Chemistry

Paul Scherrer Institut
Department of Biology and Chemistry
OFLC 109
CH-5232 Villigen PSI
Phone: +41 56 310 42 65
Fax: +41 56 310 21 99


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