Konformationsänderungen von repeat Proteinen

The modular architecture of repeat proteins determines the molecular folding mechanism of this class of proteins. Anykrin repeat (AR) proteins are a huge class proteins, which are mainly involved in protein-protein interactions. According to differences in the thermodynamic stability of single repeats, different folding mechanisms have been proposed. Nature uses these differences in stability to control function. Changes of the folding mechanism upon phosphorylation of p19INK4d and gankyrin will be elucidated. Conformational transitions of the protein structure will be studied by small angle X-ray scattering, high resolution NMR spectroscopy and accompanying molecular dynamic simulations. In parallel, binding of phosphorylated p19INK4d to CDK4/6 as well as ubiquitinylation will be examined in vitro to understand the functional consequences.