Over the last couple of years, several model systems have emerged which have found widespread use in the area of protein folding and design. One such protein is the small protein GB1. It has been employed in numerous studies, both from an experimental as well as theoretical perspective. Its structure has been determined by NMR and X-ray crystallography, and we have a long-standing program dissecting basic principles of folding, structure and stability. The structural plasticity of the hydrophobic core was examined by creating a library of core mutants, yielding surprising, novel quaternary three-dimensional protein architectures. For example, domain-swapped dimers, side-by-side dimers and a completely intertwined tetrameric protein were found.
Furthermore, structural and chemical causes for protein aggregation, such as observed in amyloids, are investigated. Important insights into protein evolution and the underlying causes for amyloid diseases such as Alzheimer’s and Parkinson’s are provided by our studies.