Dynamic structure of a multi-domain protein

Proteins in their native environment exist as a dynamic ensemble of diverse conformations. An important focus of this work was on the development of a novel approach that provides dynamic structural ensembles of multi-domain proteins. It is based on a global analysis of time-correlated distance distributions obtained via single-molecule Forster resonance energy transfer (FRET). Applying this hybrid approach to the heat shock protein 90 (Hsp90) enabled disentangling nested local and global conformational changes and revealed new mechanistic insights. A novel microfluidic device and an innovative optical setup are further technological achievements that were designed for detecting transient protein-protein interactions and dynamic multi-protein complexes.