Integrating Ion Mobility – Mass Spectrometry with Macromolecular Modeling

The recent explosion in proteomics data has left the community with detailed interaction maps and an overwhelming amount of new structural biology targets. Using IM-MS techniques that define the connectivity and stoichiometry of a complex through the generation of sub-complexes, our group has developed robust methods for generating topology models of large protein complexes. By virtue of nano-electrospray ionization (nano-ESI) we are able to accurately determine the protein complex stoichiometry based on detailed mass measurements. With solution phase disruption techniques as well as gas-phase manipulation, such as collision induced dissociation and charge manipulation strategies, we can gain connectivity information of the complexes. Iterative measurements of sub-complex stoichiometry and composition allow us to generate 2D contact diagrams for unknown protein complexes. Furthermore, by using highly accurate ion mobility measurements, the orientationally-averaged sizes of both intact and dissociated complexes can be used to produce distance and angle restraints for each subunit within a given assembly.



Contact

Ruotolo Group
University of Michigan
Department of Chemistry
Room 4550
930 N. University Ave, Ann Arbor, MI 48109-1055

Phone: (+1) 734-763-2443
Fax: (1+) 734-615-3718