AI Article Synopsis

  • The text discusses how protein function is influenced by post-translational modifications (PTMs) and their interactions, known as PTM cross-talk.
  • A new database called TCellXTalk has been developed to facilitate the identification of co-modified peptides in human T cells, specifically focusing on phosphorylation, ubiquitination, and acetylation.
  • TCellXTalk has been proven effective in a study that identified 15 co-modified peptides in T-cell receptor complex proteins, providing insights into the dynamics of these modifications during T cell activation.

Article Abstract

Motivation: Protein function is regulated by post-translational modifications (PTMs) that may act individually or interact with others in a phenomenon termed PTM cross-talk. Multiple databases have been dedicated to PTMs, including recent initiatives oriented towards the in silico prediction of PTM interactions. The study of PTM cross-talk ultimately requires experimental evidence about whether certain PTMs coexist in a single protein molecule. However, available resources do not assist researchers in the experimental detection of co-modified peptides.

Results: Herein, we present TCellXTalk, a comprehensive database of phosphorylation, ubiquitination and acetylation sites in human T cells that supports the experimental detection of co-modified peptides using targeted or directed mass spectrometry. We demonstrate the efficacy of TCellXTalk and the strategy presented here in a proof of concept experiment that enabled the identification and quantification of 15 co-modified (phosphorylated and ubiquitinated) peptides from CD3 proteins of the T-cell receptor complex. To our knowledge, these are the first co-modified peptide sequences described in this widely studied cell type. Furthermore, quantitative data showed distinct dynamics for co-modified peptides upon T cell activation, demonstrating differential regulation of co-occurring PTMs in this biological context. Overall, TCellXTalk facilitates the experimental detection of co-modified peptides in human T cells and puts forward a novel and generic strategy for the study of PTM cross-talk.

Availability And Implementation: TCellXTalk is available at https://www.tcellxtalk.org. Source Code is available at https://bitbucket.org/lp-csic-uab/tcellxtalk.

Supplementary Information: Supplementary data are available at Bioinformatics online.

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http://dx.doi.org/10.1093/bioinformatics/bty805DOI Listing

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