The knowledge of the structures of biological macromolecules is invaluable to elucidate the mechanistic details of their function. Complexes that are associated to lipid membranes carry out many important cellular functions, but their structures are largely elusive to date because these types of macromolecules are extremely difficult to assess by established experimental techniques such as X-ray crystallography and NMR spectroscopy. Our group aims to unravel the structures of membrane-associated complexes using cryoelectron tomography (CET) and subsequent modeling. CET is currently the only generally applicable three-dimensional (3D) imaging method to retrieve the density of a given complex in its close-to-native state, and the technique is therefore uniquely suited to provide density maps of membrane-associated complexes. Subsequent modeling allows determining those structures, which are compatible with the densities, but also all other available information on the complex such as biochemical interactions. The developed methodology will be applied to the complex that governs endoplasmic reticulum mediated decay of proteins (ERAD). Removal of erroneous proteins from the endoplasmic reticulum and subsequent degradation via ERAD is essential for cellular function. Malfunctions of protein degradation have been implicated in diseases such as Alzheimer and Parkison’s disease.

 

Contact: Dr. Friedrich Förster

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