In recent years, it has become evident that structural characterization would gain significantly in terms of biological relevance if framed within a cellular context, while still maintaining the atomic resolution. Therefore, major efforts have been devoted to developing Cellular Structural Biology approaches. In this respect, in-cell NMR can provide and has provided relevant contributions to the field, not only to investigate the structural and dynamical properties of macromolecules in solution but, even more relevant, to understand functional processes directly in living cells and the factors that modulate them, such as exogenous molecules, partner proteins, and oxidative stress. In this commentary, we review and discuss some of the main contributions to the understanding of protein structural and functional properties achieved by in-cell NMR.

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