Decoding protein modifications using top-down mass spectrometry

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Top-down mass spectrometry is an emerging technology which strives to preserve the post-translationally modified forms of proteins present in vivo by measuring them intact, rather than measuring peptides produced from them by proteolysis. The top-down technology is beginning to capture the interest of biologists and mass spectrometrists alike, with a main goal of deciphering interaction networks operative in cellular pathways. Here we outline recent approaches and applications of top-down mass spectrometry as well as an outlook for its future.

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Figure 1: The use of top-down MS for PTM detection: top-down characterization of a hypothetical protein and its PTMs from different cell states.
Figure 2: Classical versus electron-based methods for fragmentation of protein and peptide ions in tandem mass spectrometry.
Figure 3: The complexities of precisely characterizing eukaryotic proteins.


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Without funding from the University of Illinois, the National Institutes of Health (GM 067193), the Packard Foundation, the Alfred P. Sloan Foundation, the Dreyfus Foundation, the Roy J. Carver Charitable Trust (04-76) and the Institute of Genomic Biology, this review would not have been possible. All these sources of support have driven the advance of top-down proteomics at the University of Illinois over the past seven years.

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