Narasimhan, Siddarth, Stephan Scherpe, Alessandra Lucini Paioni, Johan van der Zwan, Gert E. Folkers, Huib Ovaa, and Marc Baldus. “DNP-Supported Solid-State NMR Spectroscopy of Proteins Inside Mammalian Cells.” Angewandte Chemie International Edition, July 19, 2019.
https://doi.org/10.1002/anie.201903246.
Elucidating at atomic level how proteins interact and are chemically modified in cells represents a leading frontier in structural biology. We have developed a tailored solid-state NMR approach that allows studying protein structure inside humans cells at atomic level under high-sensitivity DNP conditions. We demonstrate the method on Ubiquitin (Ub) which is criticially involved in cellular functioning. Our results pave the way for structural studies of larger proteins or protein complexes inside human cells which have remained elusive for in-cell solution-state NMR due to molecular size limitations.