Schlierf Group - (Membrane) Protein Folding
Membrane protein folding and insertion
Membrane proteins are key players in the functioning of cells. They are located at the interface between the inside and outside of cells and compartments. Precise folding and occupation of the accurate tertiary structure within the membrane is crucial for their correct functioning and can be considerably influenced by the surrounding lipid composition. Already single point mutations in the amino acid chain can lead to severe structural changes and diseases, like cystic fibrosis. Their hydrophobic nature and the often complex lipidic environment creates technical challenges to study folding and insertion processes.We develop methods to study folding and unfolding of membrane proteins in lipid environments using single-molecule FRET. We aim to characterize the unfolded and folded states of alpha-helical and beta-barrel proteins.
Team members on the project: Georg, Andreas, Pablo, Antoine
- Hartmann, Krainer, Keller, Schlierf (2015) Quantification of Millisecond Protein-Folding Dynamics in Membrane-Mimetic Environments by Single-Molecule FRET Spectroscopy, Analytical Chemistry
Downhill folding in slow motion
Protein folding is a process of molecular self-assembly during which a disordered polypeptide chain collapses to form a compact and well-defined three-dimensional structure. The process of folding is described as a path on a multi-dimensional energy landscape. If at each folding step along the path a decrease of entropy is nearly compensated by a decrease of enthalpy, these proteins are termed downhill folders and display ultrafast kinetics. Studying downhill folders allows understanding of fundamental principles of folding by resolving intramolecular dynamics in a step-by-step manner. We conduct a comparative study on single-molecule protein folding using optical tweezers that provide the possibility to measure structural dynamics with submillisecond and nanometer resolution.
Team members on the project: Ann, Andreas
Protein degradation observed with smFRET
A precise and tight control of the proteostasis is key for living cells. To date, mechanistic insights of the protein degradation machinery are still missing. These intricate cellular machines have to mechanically unfold their target proteins, before subsequent degradation of the unstructured polypeptide chain. The mechanical unfolding most likely requires large conformational changes inferred from crystal structures with different cofactors. We are interested in establishing a single-molecule assay to test the function of these protein unfolding machines in detail.
Team members on the project: Martine, Philip