Sensitive and High-Throughput Exploration of Protein N-Termini by TMT-TAILS N-Terminomics

Konstantinos Kalogeropoulos, Louise Bundgaard, Ulrich auf dem Keller*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingBook chapterResearchpeer-review

Abstract

Terminal amine isotopic labeling of substrates (TAILS) is a sensitive and robust quantitative mass spectrometry (MS)-based proteomics method used for the characterization of physiological or proteolytically processed protein N-termini, as well as other N-terminal posttranslational modifications (PTMs). TAILS is a well-established, high-throughput, negative enrichment workflow that enables system-wide exploration of N-terminomes independent of sample complexity. TAILS makes use of amine reactivity of free N-termini and a highly efficient aldehyde-functionalized polymer to deplete internal peptides generated after proteolytic digestion during sample preparation. Thereby, it enriches for natural N-termini, allowing for unbiased and complete investigation of differential proteolysis, protease substrate discovery, and analysis of N-terminal PTMs. In this chapter, we provide a state-of-the-art protocol, with detailed steps in all parts of the TAILS sample preparation, MS analysis, and post-processing of acquired data.
Original languageEnglish
Title of host publicationMass Spectrometry-Based Proteomics
EditorsKris Gevaert
Number of pages25
Volume2718
PublisherSpringer
Publication date2023
Pages111-135
Chapter7
ISBN (Print)978-1-0716-3456-1, 978-1-0716-3459-2
ISBN (Electronic)978-1-0716-3457-8
DOIs
Publication statusPublished - 2023
SeriesMethods in Molecular Biology
Number2718
ISSN1064-3745

Keywords

  • Mass-spectrometry-based proteomics
  • N-terminomics
  • Degradomics
  • Protease characterization
  • Protease substrate discovery
  • N-terminal posttranslational modifications
  • TAILS

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