Label-Free Method Development for Hydroxyproline PTM Mapping in Human Plasma Proteome

Post-translational modifications (PTMs) impart structural heterogeneities that can alter plasma proteins' functions in various pathophysiological processes. However, the identification and mapping of PTMs in untargeted plasma proteomics is still a challenge due to the presence of diverse compon...

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Bibliographic Details
Published in:The Protein Journal 2021-10, Vol.40 (5), p.741-755
Main Authors: Dutta, Debabrata, Rahman, Shakilur, Bhattacharje, Gourab, Bag, Swarnendu, Sing, Bidhan Chandra, Chatterjee, Jyotirmoy, Basak, Amit, Das, Amit Kumar
Format: Article
Language:English
Subjects:
Animal Anatomy
Biochemistry
Bioorganic Chemistry
Blood plasma
Blood Proteins - analysis
Blood Proteins - metabolism
Chemistry
Chemistry and Materials Science
Chromatography, Liquid
Histology
Humans
Hydroxylation
Hydroxyproline
Hydroxyproline - analysis
Hydroxyproline - metabolism
Mass spectrometry
Mass spectroscopy
Molecular dynamics
Morphology
Organic Chemistry
Peptide mapping
Peptides
Plasma
Plasma proteins
Post-translation
Proline
Protein Processing, Post-Translational
Proteins
Proteome - analysis
Proteome - metabolism
Proteomes
Proteomics
Simulation analysis
Tandem Mass Spectrometry
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Summary:Post-translational modifications (PTMs) impart structural heterogeneities that can alter plasma proteins' functions in various pathophysiological processes. However, the identification and mapping of PTMs in untargeted plasma proteomics is still a challenge due to the presence of diverse components in blood. Here, we report a label-free method for identifying and mapping hydroxylated proteins using tandem mass spectrometry (MS/MS) in the human plasma sample. Our untargeted proteomics approach led us to identify 676 de novo sequenced peptides in human plasma that correspond to 201 proteins, out of which 11 plasma proteins were found to be hydroxylated. Among these hydroxylated proteins, Immunoglobulin A1 (IgA1) heavy chain was found to be modified at residue 285 (Pro 285 to Hyp 285 ), which was further validated by MS/MS study. Molecular dynamics (MD) simulation analysis demonstrated that this proline hydroxylation in IgA1 caused both local and global structural changes. Overall, this study provides a comprehensive understanding of the protein profile containing Hyp PTMs in human plasma and shows the future perspective of identifying and discriminating Hyp PTM in the normal and the diseased proteomes.
ISSN:1572-3887
1573-4943
1875-8355
DOI:10.1007/s10930-021-09984-7