The research group „Macromolecular Interactions“ studies the structure-function relationships of functional amyloids and aggregates formed by bacteria, fungi and viruses, and the mechanism of their formation.
Protein aggregates are usually viewed as the undesirable products of protein misfolding events. Some of the most wide-spread protein misfolding diseases, such as Alzheimer’s or Parkinson’s disease, are characterized by the aggregation of normal cellular proteins into amyloid fibrils. Amyloids formed by different proteins share some common biophysical properties, including a characteristic intermolecular beta-sheet structure. Amyloids are also able to form prions – these are infectious proteins that cause fatal diseases like BSE („mad cow’s disease“) or Creutzfeld Jakob Disease.
Only recently it has been discovered that amyloid fibrils also constitute the normal, functional conformation of a growing number of proteins. This fold appears to be employed mostly, but not exclusively, by bacteria and fungi. Some of these amyloids are also prions, and they thus offer themselves to establish structure-function relationships of prions in safe and easy to handle microbial systems.
Several unrelated functional amyloids also form protein coats on the surfaces of bacteria and fungi. These coats have multiple functions, including host attachment and invasion. Surface amyloids are particularly interesting because some of them have been found on common human pathogens and have been shown to enhance their virulence. It is our goal to establish the structural basis for the function of these amyloids, and their mode of interaction with specific host proteins.
High-resolution structural information is a prerequisite to understand the mechanism of amyloid and prion formation. However, amyloids are inherently difficult to study by established techniques in structural biology. We therefore use a modular approach that uses several different biophysical techniques and mutagenesis approaches to obtain the necessary information for structure calculations. Of central importance in this process is quenched hydrogen exchange measured by Nuclear Magnetic Resonance (qH/D NMR). NMR is also our major tool to study protein-protein interactions in solution.
