Periodic Reporting for period 2 - SPICE (Spectroscopy in cells with tailored in-vivo labelling strategies and multiply addressable nano-structural probes)
Reporting period: 2019-12-01 to 2021-05-31
Intrinsically disordered proteins (IDPs), implicated in human diseases, among them prominently cancers, cardiovascular diseases, diabetes and neurodegenerative diseases, adopt a rich variety of different conformations depending on the macromolecular context. In order to unravel their pathophysiological role, monitoring their intracellular conformational states and identifying differences for the disease variants is crucial.
Therefore, the Drescher group pushes the experimental conditions from in vitro experiments towards structure determination in vivo.
Therefore, the team incorporated genetically encoded, artificial amino acids into proteins and used them as targets for their labels.
For the first time, they combined in-cell labeling and in-cell EPR spectroscopy. The combination of intracellular bioorthogonal labeling with in-cell EPR measurements does not require additional purification or delivery steps of spin-labeled protein to the cells.
The Drescher group also applied EPR spectroscopy to study aggregation of the microtubule-associated protein Tau, which is a hallmark of Alzheimer’s disease. They found that the interaction with Hsp90 promotes an open Tau conformation, which they identified as the molecular basis for the formation of small Tau oligomers.