Table 1. Characterization of higher order protein structure by MS.

Specific features of protein higher order structure	Does the analysis require alterations in the protein environment?
	protein environment is significantly altered (transfer to a volatile solvent system is required)	protein environment should not be altered to ensure its integrity
Secondary and ternary structure: overall physical dimensions/compactness	Direct ESI MS: analysis of protein ion charge state distributions [7]
Secondary and ternary structure: protein backbone flexibility maps	HDX MS	HDX MS
Ternary structure: integrity of disulfide networks		Disulfide bond mapping [61]
Ternary structure: side chain solvent exposure maps		Photo- [62], radiolytic [63], oxidative [64] and selective chemical [65] labeling
Quaternary structure: composition and stoichiometry of non-covalent assemblies	Direct ESI MS [8]	Chemical cross-linking [66]
Quaternary structure: inter-subunit interfaces	HDX MS	HDX MS; chemical cross-linking; chemical labeling
Interaction with physiological partners	Direct ESI MS [32, 67]	Chemical cross-linking