Proteomics

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TCellXTalk enables the detection of co-modified peptides for the study of protein post-translational modification cross-talk in T cells


ABSTRACT: 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 to the in silico prediction of PTM interactions. The study of PTM cross-talk ultimately requires experimental evidence about whether certain PTMs co-exist in a single protein molecule. However, available resources do not assist researchers in the experimental detection of co-modified peptides. Here 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 in 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 of co-modified peptides upon T cell activation, demonstrating differential regulation of co-occurring PTMs in this biological context. Overall, TCellXTalk enables 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.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Primary Cell, T Cell

SUBMITTER: Montserrat Carrascal  

LAB HEAD: Montserrat Carrascal

PROVIDER: PXD010176 | Pride | 2018-09-19

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
310_IAP_Ac_bRP_FrA_30.raw Raw
310_IAP_Ac_bRP_FrB_30.raw Raw
310_IAP_Ac_bRP_FrC_30.raw Raw
310_IAP_Ac_bRP_FrD_30.raw Raw
310_IAP_Ac_bRP_FrE_30.raw Raw
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TCellXTalk facilitates the detection of co-modified peptides for the study of protein post-translational modification cross-talk in T cells.

Casanovas Albert A   Gallardo Óscar Ó   Carrascal Montserrat M   Abian Joaquin J  

Bioinformatics (Oxford, England) 20190401 8


<h4>Motivation</h4>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 r  ...[more]

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