Alternate Dissociation Pathways Identified in Charge-Reduced Protein Complex Ions

摘要

In recent years tandem mass spectrometry (MS) of large protein complexes has proven to be capable of assessing the stoichiometry, connectivity, and structural details of multi-protein assemblies. In order to obtain such information it is crucial to activate and dissociate the assembly in a predictable way. Usually this is achieved by collision induced dissociation (CID) which involves two characteristic events: (I) stepwise unfolding of one of the complexes subunits (Figure 1) and (II) subsequent dissociation into a low-charged (n-1)mer and a highly-charged, unfolded monomer. However, recent investigations provided evidence that some protein complexes may dissociate following very different mechanisms. To shed further light on the forces that dictate the mechanistic route taken for a given protein complex dissociation, we analyzed systematically the charge state dependent CID behavior of tetra-meric human transthyretin (TTR) by both tandem mass spectrometry and ion mobility mass spectrometry (IM-MS).