Open AccessTargeted in situ cross-linking mass spectrometry and integrative modeling reveal the architectures of three proteins from SARS-CoV-2
Author(s) -
Moriya Slavin,
Joanna Zamel,
Keren Zohar,
Tsiona Eliyahu,
Merav Braitbard,
Esther S. Brielle,
Lea Baraz,
Miri Stolovich-Rain,
Ahuva Friedman,
Dana Wolf,
Alexander Rouvinski,
Michal Linial,
Dina Stroopinsky,
Nir Kalisman
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2103554118
Subject(s) - in situ , mass spectrometry , computational biology , covid-19 , chemistry , biology , chromatography , medicine , virology , disease , organic chemistry , pathology , infectious disease (medical specialty) , outbreak
Significance We present a generic methodology that extracts structural data from living, intact cells for any protein of interest. Application of this methodology to different viral proteins resulted in significant cross-link sets that revealed the connectivity within their structures. Importantly, we show that these cross-link sets are detailed enough to enable the integrative modeling of the full-length protein sequence. Consequently, we report the global structural organization of Nsp2 and the dimer of the nucleocapsid protein. We foresee that similar applications will be highly useful to study other recalcitrant proteins on which the mainstream structural approaches currently fail.