Constructing Proteoform Families in Mammalian Systems
Proteoforms are the different forms of proteins produced from the same gene as a result of genetic variations, RNA splice variants, and post-translational modifications (PTMs). A proteoform family is the set of proteoforms from a single gene. Because different proteoforms can perform different functions in cells, proteoform identification and quantification is essential for understanding a biological system. The Lloyd Smith group at the University of Wisconsin-Madison has recently developed a proteoform identification strategy which constructs and identifies proteoforms families by performing intact-only mass spectrometric analysis of proteins. I am working on a few areas in this proteoform technology development. Several Smith lab members and I are creating software to automate the construction, quantification, and visualization of proteoform families. I am working to incorporate existing proteomic strategies, which use fragmentation of proteins or peptides to make identifications, into our software for a more comprehensive analysis. I am also extending this technology to mammalian systems, beginning with mitochondrial proteoforms.
Schaffer, L. V.; Shortreed, M. R.; Cesnik, A. C.; Frey, B. L.; Solntsev, S. K.; Scalf, M.; Smith, L. M. Expanding Proteoform Identifications in Top-Down Proteomic Analyses by Constructing Proteoform Families. Analytical Chemistry 2018, 90 (2), 1325-1333.
Cesnik, A. J.; Shortreed, M. R.; Schaffer, L. V.; Frey, B. L.; Knoener, R.; Scalf, M.; Soltznev, S. K.; Smith, L. M. Construction, Visualization, and Quantification of Proteoform Families. Journal of Proteome Research 2018, 17(1), 568-578.
Dai, Y.; Shortreed, M.R.; Scalf, M.; Frey, B.L.; Cesnik, A.J.; Solntsev, S.K.; Schaffer, L.V.; Smith, L.M. Elucidating E. coli Proteoform Families Using Intact-Mass Proteomics and a Global PTM Discovery Database. Journal of Proteome Research 2017, 16(11), 4156-4165.