'Looking at proteins in live cells with atomic resolution: from Science Fiction to Science Reality'

Most proteins function inside cells and in environments that are vastly different from the experimental in vitro setups we typically use to characterize them. So what do proteins actually look like inside live cells? Although this question may seem naive, it is far from being answered easily. This is largely due to the physical requirements of most Structural Biology methods, which are incompatible with intact cellular samples. Here, I outline the use of solution-state NMR spectroscopy to derive atomic-resolution insights into the structure and function of proteins in eukaryotic cells. Specifically, I describe how we employ in-cell NMR spectroscopy to study biological activities ranging from post-translational protein modifications in response to cell signaling, to the formation of intracellular amyloid aggregates during neurodegenerative disease processes.