Wenzel Gaßner

Master student


Universitätsstraße 32
70569 Stuttgart


PIP2: Another player in biased signaling of G protein-coupled receptors?
The ability of a cell to react to extracellular stimuli is enabled by a complex protein machinery based on G protein-coupled receptors (GPCRs) attached to the cell membrane and their intracellular interaction partners, G-proteins and arrestins. Due to their important roles in healthy and disease states, GPCRs are targeted by one third of all current drugs.
Complementing the atomic-force-microscopy investigations of Florian Wilhelm in the group of Prof. Daniel J. Müller at the ETH Zürich, we study the binding of PIP2, a lipidic messenger, to the β2-adrenergic receptor/β-arrestin2 complex and its impact on the complex structure and dynamics. Also, we mechanically separate β-arrestin2 from the receptor to unravel the relative stability of the complexes, the dissociation pathways, and the importance of individual residues. This knowledge is of particular pharmacological importance, as currently only the activation state of the receptor is targeted by pharmaceuticals. However, arrestin binding to the receptor competes with binding of its cognate G protein and causes receptor desensitization, thus opening new pathways for pharmacological intervention.

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