“…Native mass spectrometry (nMS) enables direct mass measurement of intact noncovalent macromolecular assemblies upon gas-phase transfer from nondenaturing solution conditions (Heck, 2008;Hernandez and Robinson, 2007;Leney and Heck, 2017;Loo, 1997). By maintaining the quaternary structure of protein assemblies, nMS has provided key complementary structural information for hybrid and integrative structural studies involving cryo-EM, including complex composition, subunit stoichiometry, intersubunit connectivity, and assembly dynamics (Abbas et al, 2020;Casanal et al, 2017;Chase et al, 2018;Geiger et al, 2010;Kuhlen et al, 2018;Liko et al, 2016;Lorenzen et al, 2007;Martinez-Rucobo et al, 2015;Snijder et al, 2017). In addition, high-resolution nMS can resolve and identify relevant post-translational modifications as well as bound ligands, cofactors, substrates, or stabilizing lipids that are useful in assigning previously unknown EM densities during structure reconstruction and refinement (Liko et al, 2016).…”