Targeted in situ cross-linking mass spectrometry and integrative modeling reveal the architectures of three proteins from SARS-CoV-2

Significance We present a generic methodology that extracts structural data from living, intact cells for any protein of interest. Application this to different viral proteins resulted in significant cross-link sets revealed the connectivity within their structures. Importantly, we show these are detailed enough enable integrative modeling full-length sequence. Consequently, report global organization Nsp2 and dimer nucleocapsid protein. foresee similar applications will be highly useful study other recalcitrant on which mainstream approaches currently fail.