NMR spectroscopy to unravel biomolecular mechanisms
Proteins and their interactions play key roles in all kinds of biological functions. We use nuclear magnetic resonance (NMR) spectroscopy to resolve structural and functional details of proteins at atomic resolution and thus unravel their molecular mechanisms.
Proteins are responsible for a wide range of essential biological functions, including signal transduction, catalysis, cellular homeostasis, metabolism and membrane transport. We characterize underlying molecular processes at atomic resolution by using NMR spectroscopy and related techniques. Part of our activities is the development of new and improved NMR techniques for challenging biomacromolecules including membrane proteins.
Chaperones are responsible for the transport of unfolded membrane proteins as part of the biosynthesis of outer membranes of bacteria and mitochondria. They also play an important role in cellular proteostasis: they ensure that proteins are functional at the right place at the right time. We employ high-resolution NMR spectroscopy to determine conformation and dynamics of large chaperone–client complexes including membrane-protein clients. We want to understand in detail how client proteins are recognized, which biophysical laws govern chaperone function and how clients are transferred between chaperones.
Outer membrane protein folding
As the last event in outer membrane biogenesis, barrel-like outer membrane proteins are folded and inserted into the outer membrane by members of the Omp85 family of proteins. The Omp85 family comprises large foldases, membrane proteins that process their substrates in an energy-independent manner. The insertion mechanism presumably includes the formation of a hybrid foldase–substrate barrel as key intermediate event. We are currently attempting to unravel the in vivo and in vitro folding mechanisms of the substrates.
The VDAC membrane protein
One example of our work is the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane. VDAC allows the passage of molecules involved in cellular energy production, such as phosphate and nucleotides. The protein also has a major role in regulating metabolism and in programmed cell death, as well as in the development of cancer. In our latest experiments we are starting to understand the molecular prerequisites for these functions.