A single protein to multiple peptides: Investigation of protein-peptide correlations using targeted alpha-2-macroglobulin analysis

Yildiz P., Ozcan S.

Talanta, cilt.265, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 265
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1016/j.talanta.2023.124878
  • Dergi Adı: Talanta
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, L'Année philologique, Aerospace Database, Analytical Abstracts, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, Communication Abstracts, Compendex, Food Science & Technology Abstracts, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Anahtar Kelimeler: Alpha-2-macroglobulin, Mass spectrometry, Quantitative proteomics, Serum, Targeted proteomics, Unique peptide
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

Özet

Recent advances in proteomics technologies have enabled the analysis of thousands of proteins in a high-throughput manner. Mass spectrometry (MS) based proteomics uses a peptide-centric approach where biological samples undergo specific proteolytic digestion and then only unique peptides are used for protein identification and quantification. Considering the fact that a single protein may have multiple unique peptides and a number of different forms, it becomes essential to understand dynamic protein-peptide relationships to ensure robust and reliable peptide-centric protein analysis. In this study, we investigated the correlation between protein concentration and corresponding unique peptide responses under a conventional proteolytic digestion condition. Protein-peptide correlation, digestion efficiency, matrix-effect, and concentration-effect were evaluated. Twelve unique peptides of alpha-2-macroglobulin (A2MG) were monitored using a targeted MS approach to acquire insights into protein-peptide dynamics. Although the peptide responses were reproducible between replicates, protein-peptide correlation was moderate in protein standards and low in complex matrices. The results suggest that reproducible peptide signal could be misleading in clinical studies and a peptide selection could dramatically change the outcome at protein level. This is the first study investigating quantitative protein-peptide correlations in biological samples using all unique peptides representing the same protein and opens a discussion on peptide-based proteomics.