TY - JOUR
T1 - Progress in Top-Down Proteomics and the Analysis of Proteoforms
AU - Toby, Timothy K.
AU - Fornelli, Luca
AU - Kelleher, Neil L.
N1 - Publisher Copyright:
Copyright © 2016 by Annual Reviews. All rights reserved.
PY - 2016/6/12
Y1 - 2016/6/12
N2 - From a molecular perspective, enactors of function in biology are intact proteins that can be variably modified at the genetic, transcriptional, or post-translational level. Over the past 30 years, mass spectrometry (MS) has become a powerful method for the analysis of proteomes. Prevailing bottom-up proteomics operates at the level of the peptide, leading to issues with protein inference, connectivity, and incomplete sequence-modification information. Top-down proteomics (TDP), alternatively, applies MS at the proteoform level to analyze intact proteins with diverse sources of intramolecular complexity preserved during analysis. Fortunately, advances in prefractionation workflows, MS instrumentation, and dissociation methods for whole-protein ions have helped TDP emerge as an accessible and potentially disruptive modality with increasingly translational value. In this review, we discuss technical and conceptual advances in TDP, along with the growing power of proteoform-resolved measurements in clinical and translational research.
AB - From a molecular perspective, enactors of function in biology are intact proteins that can be variably modified at the genetic, transcriptional, or post-translational level. Over the past 30 years, mass spectrometry (MS) has become a powerful method for the analysis of proteomes. Prevailing bottom-up proteomics operates at the level of the peptide, leading to issues with protein inference, connectivity, and incomplete sequence-modification information. Top-down proteomics (TDP), alternatively, applies MS at the proteoform level to analyze intact proteins with diverse sources of intramolecular complexity preserved during analysis. Fortunately, advances in prefractionation workflows, MS instrumentation, and dissociation methods for whole-protein ions have helped TDP emerge as an accessible and potentially disruptive modality with increasingly translational value. In this review, we discuss technical and conceptual advances in TDP, along with the growing power of proteoform-resolved measurements in clinical and translational research.
KW - Intact protein analysis
KW - Mass spectrometry
KW - Proteoforms
KW - Top-down proteomics
KW - Translational proteomics
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U2 - 10.1146/annurev-anchem-071015-041550
DO - 10.1146/annurev-anchem-071015-041550
M3 - Review article
C2 - 27306313
AN - SCOPUS:84975467064
SN - 1936-1327
VL - 9
SP - 499
EP - 519
JO - Annual Review of Analytical Chemistry
JF - Annual Review of Analytical Chemistry
ER -