Welcome to the Riek group


The aim of the research in our lab is to understand the conformational switches of proteins with particular emhpasis on amyloid disease and trans-membrane signaling. We use a variety of techniques to solve the structures and to study the conformational transition of amyloidogenic proteins and membrane proteins including as a major experimental tool Nuclear Magnetic Resonance Spectroscopy (NMR).

abeta3.jpgAlzheimer and prion diseases belong to amyloid diseases for which a normal host polypeptide accumulates in an abnormal beta-sheet -rich form in fibrillar aggregates. In prion diseases, the mostly alpha-helical host prion protein undergoes a conformational switch to a structure with enhanced beta-sheet content. It is believed that this converted abnormal form of the prion protein is the infectious agent of bovine spongiform encephalopathy (BSE), scrapie in sheep and Creutzfeldt-Jakob disease (CJD) in humans. In Alzheimer's disease, a peptide with mostly 'random-coil' like structure is converted to a beta-sheet-rich polypeptide clustered in fibrils. These fibrils are toxic to cells. Furthermore, the phenotypes of the well characterized yeast prions [PSI] and [URE3] and the prion phenotype [HET-s] in Podospora anserina are associated with amyloid formation. Since in all mentioned systems the polypeptides involved undergo a structural transition, detailed knowledge of the structures and dynamics of the normal and abnormal conformers and of the conformational transitions themselves are important aims of our work.

NMR is one of the principal experimental techniques in structural biology with abilities to determine atomic resolution structures as well as to investigate dynamic features and intermolecular interactions of biological macromolecules with a molecular weight smaller than 30 kDa. With the novel techniques TROSY and CRIPT, NMR is the multiprobe method to study protein-protein or protein-drug interactions of structures with a molecular weight up to 1 MDa. Immediate applications at our lab include NMR studies of membrane proteins. 1/3 of all proteins are membrane protens, but from the 30'000 protein structures deposited in the pdb data base only about 100 are membrane protein structures. Hence, structural characterization of membrane proteins are very important.

Curriculum vitae