title: The role of salt bridges, charge density, and subunit flexibility in determining disassembly routes of protein complexes.
abstract: Mass spectrometry can be used to characterize multiprotein complexes, defining their subunit stoichiometry and composition following solution disruption and collision-induced dissociation (CID). While CID of protein complexes in the gas phase typically results in the dissociation of unfolded subunits, a second atypical route is possible wherein compact subunits or subcomplexes are ejected without unfolding. Because tertiary structure and subunit interactions may be retained, this is the preferred route for structural investigations. How can we influence which pathway is adopted? By studying properties of a series of homomeric and heteromeric protein complexes and varying their overall charge in solution, we found that low subunit flexibility, higher charge densities, fewer salt bridges, and smaller interfaces are likely to be involved in promoting dissociation routes without unfolding. Manipulating the charge on a protein complex therefore enables us to direct dissociation through structurally informative pathways that mimic those followed in solution.
authors.affiliation: Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, Oxford OX1 3QZ, UK.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Hall
authors.forename: Helena
authors.initials: H
authors.lastname: Hernández
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Marsh
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Teichmann
authors.forename: Carol V
authors.initials: CV
authors.lastname: Robinson
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000737:chemistry; D011228:Prealbumin / Q000737:chemistry*; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry*; D058767:Protein Unfolding; D011817:Rabbits; D000683:Serum Amyloid P-Component / Q000737:chemistry*
chemical_list: D046912:Multiprotein Complexes; D011228:Prealbumin; D021122:Protein Subunits; D000683:Serum Amyloid P-Component