Kristyna Pluhackova Presents Research at Pharmaceutical Colloquium in Marburg

July 9, 2024

[Picture: Kristyna Pluhackova]

Dr. Kristyna Pluhackova, a junior research group leader at SimTech, recently presented her latest research findings at the Pharmaceutical Colloquium of the Philipps-University Marburg. Invited by the German Pharmaceutical Society (DPhG), Dr. Pluhackova delivered an insightful lecture on "Interactions of β-arrestin2 with β2-adrenergic Receptor: Expected and Unexpected Quantitative Insights from Atomic Force Microscopy and Molecular Dynamics Simulations". She explored the complex world of G protein-coupled receptors (GPCRs). These receptors are vital for signal transduction across cell membranes and are the target of over 30% of all marketed drugs.

The forces upon mechanical separation of arrestin (shown as green cartoon) from membrane-embedded receptor (shown as rainbow-colored cartoon) are recorded and compared using molecular dynamics simulations and single-molecule atomic force microscopy.

Her research focuses on the β2-adrenergic receptor, a well-characterized GPCR, and its interaction with β-arrestin2. Using a combination of molecular dynamics simulations and single-molecule atomic force microscopy, Dr. Pluhackova and her experimental collaborators at the ETH Zürich quantified the binding strength between these two proteins under various conditions. This approach enabled them to distinguish individual interaction modes, such as the arrestin binding to the phosphorylated C-terminus and the intracellular binding pocket of the receptor.

Additionally, their research revealed different pathways of stable complex formation and identified the competitive effect of PIP2 lipids—a minor phospholipid component of the plasma membrane's inner leaflet and a substrate for several signaling proteins—with receptor phosphorylation. These findings provide significant insights into the molecular mechanisms governing GPCR/arrestin interactions, offering valuable information with considerable pharmacological interest.

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