The role of salt bridges, charge density, and subunit flexibility in determining disassembly routes of protein complexes

Structure. 2013 Aug 6;21(8):1325-37. doi: 10.1016/j.str.2013.06.004. Epub 2013 Jul 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Humans
  • Molecular Dynamics Simulation*
  • Multiprotein Complexes / chemistry
  • Prealbumin / chemistry*
  • Protein Interaction Domains and Motifs
  • Protein Stability
  • Protein Structure, Quaternary
  • Protein Subunits / chemistry*
  • Protein Unfolding
  • Rabbits
  • Serum Amyloid P-Component / chemistry*


  • Multiprotein Complexes
  • Prealbumin
  • Protein Subunits
  • Serum Amyloid P-Component