Department of Molecular Biophysics (Adam Lange)

Figure 1: Magic-angle spinning rotors used in our lab. The smallest rotors with an outer diameter of 1.3 mm can be spun at a rate of up to 65,000 rotations per second. The fast rotation mimics the situation of tumbling molecules in solution and allows us to record high-resolution NMR spectra in the solid state.

   We study protein structure and dynamics by nuclear magnetic resonance in the solid state (solid-state NMR) and a variety of other biophysical methods. In the last decade, solid-state NMR has emerged as a powerful technique in structural biology as it gives access to structural information for systems which are insoluble or do not crystallize easily. For instance, membrane proteins in a lipid bilayer environment or supramolecular assemblies such as the needle of the type three secretion system (T3SS), which are composed of multiple copies of a single small protein, can be readily studied.

   For solid-state NMR investigations, samples are placed in a strong superconducting magnet (external field up to 20 T, i.e.  400,000 times as strong as the earth’s magnetic field) and spun rapidly (ca. 10,000 rotations per second). This rotation around an axis that is inclined to the magnetic field by a “magic angle” of 54.7° emulates the situation of fast and freely tumbling molecules in solution. By means of this magic-angle spinning, high resolution and sensitivity can be reached in the NMR spectra of solid proteins.

   A main focus of our group is on bacterial supramolecular protein assemblies including T3SS needles, the type I pilus, and cytoskeletal bactofilin filaments. Furthermore, we are interested in the study of membrane proteins, such as amino acid transporters and ion channels. In comparison to X-ray crystallography and cryo-electron microscopy that have recently shown impressive successes in determining membrane protein structures, solid-state NMR has the advantage that the protein of interest can be studied in a physiological lipid environment at room temperature. In addition to protein structure, NMR spectroscopy is very well suited to study protein dynamics, which are often directly related to protein function.

   In terms of solid-state NMR method development, the focus in our lab is on new experiments for efficient and easy sequential resonance assignment. For example, we have introduced a set of proton-detected 3D experiments based on dipolar out-and-back transfers and applied it to deuterated T3SS needles. Furthermore, we exploit novel isotope-labeling schemes that enhance spectral resolution and facilitate the detection of long-range distance restraints.

Figure 2: Schematic representation of the type three secretion system (T3SS). The structure of the needle was recently determined by our group using a combination of solid-state NMR, electron microscopy and computer modelling.
Figure 3: View through the T3SS needle. The schematic representation of the needle subunits corresponds to the solid-state NMR model that we elucidated.

Leibniz-Institut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
Campus Berlin-Buch
Robert-Roessle-Str. 10
13125 Berlin, Germany
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