Developments in MS enable us to apply this technique to non-covalent complexes, defining their stoichiometry, subunit interactions and architectural organization. We illustrate the application of this non-covalent MS approach to uncovering the overall topological arrangements of subunits and interactions within RNA–protein complexes studied in our laboratory over the last 5 years. These studies exemplify the emerging role and potential of MS as a complementary structural biology methodology and demonstrate its unique niche in investigations of dynamic or heterogeneous protein–nucleic acid complexes, which are not accessible to classical high-resolution structural biology techniques.

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