Cellular solid-state NMR on large prokaryotic and eukaryotic membrane protein complexes

Unraveling the structure and dynamics of biomolecules is pivotal to understand their function. Hitherto, structural biology has been dependent on data obtained under in-vitro circumstances thereby neglecting the influence of the natural environment. Here, we developed a solid-state Nuclear Magnetic Resonance (ssNMR) approach, the so-called Cellular ssNMR, supported by Dynamic Nuclear Polarization (DNP) to investigate large membrane protein complexes in their native settings at atomic level. First, we examine the large bacterial membrane protein complex, namely, the type IV secretion system core complex in the bacterial cell envelope. Furthermore, we extend our NMR-based approach to scrutinize the large eukaryotic protein, Epidermal Growth Factor Receptor (EGFR) in membrane vesicles derived from eukaryotic cells. The results presented in this thesis show the power of DNP-supported ssNMR to investigate protein complexes at atomic resolution in native cellular settings.