Nanoproteomics enables proteoform-resolved analysis of low-abundance proteins in human serum
Open Access
- 6 August 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-12
- https://doi.org/10.1038/s41467-020-17643-1
Abstract
Top-down mass spectrometry (MS)-based proteomics provides a comprehensive analysis of proteoforms to achieve a proteome-wide understanding of protein functions. However, the MS detection of low-abundance proteins from blood remains an unsolved challenge due to the extraordinary dynamic range of the blood proteome. Here, we develop an integrated nanoproteomics method coupling peptide-functionalized superparamagnetic nanoparticles (NPs) with top-down MS for the enrichment and comprehensive analysis of cardiac troponin I (cTnI), a gold-standard cardiac biomarker, directly from serum. These NPs enable the sensitive enrichment of cTnI (1010 more abundant than cTnI). We demonstrate that top-down nanoproteomics can provide high-resolution proteoform-resolved molecular fingerprints of diverse cTnI proteoforms to establish proteoform-pathophysiology relationships. This scalable and reproducible antibody-free strategy can generally enable the proteoform-resolved analysis of low-abundance proteins directly from serum to reveal previously unachievable molecular details.Funding Information
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (HL007936-19)
- U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD018475, OD018475, OD018475, OD018475)
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (GM117058, GM125085, GM125085, GM117058, GM117058, GM117058, GM125085)
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
- U.S. Department of Health & Human Services | NIH | NIH Office of the Director
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
- U.S. Department of Health & Human Services | NIH | NIH Office of the Director
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
- U.S. Department of Health & Human Services | NIH | NIH Office of the Director
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