title: Salt Bridge Rearrangement (SaBRe) Explains the Dissociation Behavior of Noncovalent Complexes.
abstract: Native electrospray ionization-mass spectrometry, with gas-phase activation and solution compositions that partially release subcomplexes, can elucidate topologies of macromolecular assemblies. That so much complexity can be preserved in gas-phase assemblies is remarkable, although a long-standing conundrum has been the differences between their gas- and solution-phase decompositions. Collision-induced dissociation of multimeric noncovalent complexes typically distributes products asymmetrically (i.e., by ejecting a single subunit bearing a large percentage of the excess charge). That unexpected behavior has been rationalized as one subunit "unfolding" to depart with more charge. We present an alternative explanation based on heterolytic ion-pair scission and rearrangement, a mechanism that inherently partitions charge asymmetrically. Excessive barriers to dissociation are circumvented in this manner, when local charge rearrangements access a lower-barrier surface. An implication of this ion pair consideration is that stability differences between high- and low-charge state ions usually attributed to Coulomb repulsion may, alternatively, be conveyed by attractive forces from ion pairs (salt bridges) stabilizing low-charge state ions. Should the number of ion pairs be roughly inversely related to charge, symmetric dissociations would be favored from highly charged complexes, as observed. Correlations between a gas-phase protein's size and charge reflect the quantity of restraining ion pairs. Collisionally-facilitated salt bridge rearrangement (SaBRe) may explain unusual size "contractions" seen for some activated, low charge state complexes. That some low-charged multimers preferentially cleave covalent bonds or shed small ions to disrupting noncovalent associations is also explained by greater ion pairing in low charge state complexes. Graphical Abstract ᅟ.
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, 90095, USA. RLoo@mednet.ucla.edu.
authors.forename: Rachel R Ogorzalek
authors.initials: RR
authors.lastname: Loo
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, 90095, USA. jloo@chem.ucla.edu.|UCLA/DOE Institute for Genomics and Proteomics, University of California-Los Angeles, Los Angeles, CA, 90095, USA. jloo@chem.ucla.edu.|Department of Chemistry and Biochemistry, University of California-Los Angeles, Los Angeles, CA, 90095, USA. jloo@chem.ucla.edu.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Loo
mesh_terms: D005740:Gases; D007477:Ions; D011506:Proteins / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D005740:Gases; D007477:Ions; D011506:Proteins
keywords: Asymmetric dissociations; Electrospray ionization; Ion pairs; Noncovalent complexes; Salt bridges; Supercharging; Tandem mass spectrometry