Relative interfacial cleavage energetics of protein complexes revealed by surface collisions.
Sophie R HarveyJustin T SeffernickRoyston S QuintynYang SongYue JuJing YanAniruddha N SahasrabuddheAndrew NorrisMowei ZhouEdward J BehrmanSteffen LindertVicki H WysockiPublished in: Proceedings of the National Academy of Sciences of the United States of America (2019)
To fulfill their biological functions, proteins must interact with their specific binding partners and often function as large assemblies composed of multiple proteins or proteins plus other biomolecules. Structural characterization of these complexes, including identification of all binding partners, their relative binding affinities, and complex topology, is integral for understanding function. Understanding how proteins assemble and how subunits in a complex interact is a cornerstone of structural biology. Here we report a native mass spectrometry (MS)-based method to characterize subunit interactions in globular protein complexes. We demonstrate that dissociation of protein complexes by surface collisions, at the lower end of the typical surface-induced dissociation (SID) collision energy range, consistently cleaves the weakest protein:protein interfaces, producing products that are reflective of the known structure. We present here combined results for multiple complexes as a training set, two validation cases, and four computational models. We show that SID appearance energies can be predicted from structures via a computationally derived expression containing three terms (number of residues in a given interface, unsatisfied hydrogen bonds, and a rigidity factor).
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