The structural and functional signatures of proteins that undergo multiple events of post-translational modification

Vikas Pejaver, Wei Lun Hsu, Fuxiao Xin, A. Dunker, Vladimir N. Uversky, Predrag Radivojac

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

The structural, functional, and mechanistic characterization of several types of posttranslational modifications (PTMs) is well-documented. PTMs, however, may interact or interfere with one another when regulating protein function. Yet, characterization of the structural and functional signatures of their crosstalk has been hindered by the scarcity of data. To this end, we developed a unified sequence-based predictor of 23 types of PTM sites that, we believe, is a useful tool in guiding biological experiments and data interpretation. We then used experimentally determined and predicted PTM sites to investigate two particular cases of potential PTM crosstalk in eukaryotes. First, we identified proteins statistically enriched in multiple types of PTM sites and found that they show preferences toward intrinsically disordered regions as well as functional roles in transcriptional, posttranscriptional, and developmental processes. Second, we observed that target sites modified by more than one type of PTM, referred to as shared PTM sites, show even stronger preferences toward disordered regions than their single-PTM counterparts; we explain this by the need for these regions to accommodate multiple partners. Finally, we investigated the influence of single and shared PTMs on differential regulation of protein-protein interactions. We provide evidence that molecular recognition features (MoRFs) show significant preferences for PTM sites, particularly shared PTM sites, implicating PTMs in the modulation of this specific type of macromolecular recognition. We conclude that intrinsic disorder is a strong structural prerequisite for complex PTM-based regulation, particularly in context-dependent protein-protein interactions related to transcriptional and developmental processes. Availability: www.modpred.org.

Original languageEnglish
Pages (from-to)1077-1093
Number of pages17
JournalProtein Science
Volume23
Issue number8
DOIs
StatePublished - 2014

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Post Translational Protein Processing
Proteins
Crosstalk
Molecular recognition
Modulation
Availability
Sexual Partners
Eukaryota
Experiments

Keywords

  • Crosstalk
  • Intrinsically disordered protein
  • Molecular recognition feature
  • MoRF
  • Post-translational modification
  • Prediction
  • Protein
  • Protein interaction
  • Steric competition

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Medicine(all)

Cite this

The structural and functional signatures of proteins that undergo multiple events of post-translational modification. / Pejaver, Vikas; Hsu, Wei Lun; Xin, Fuxiao; Dunker, A.; Uversky, Vladimir N.; Radivojac, Predrag.

In: Protein Science, Vol. 23, No. 8, 2014, p. 1077-1093.

Research output: Contribution to journalArticle

Pejaver, Vikas ; Hsu, Wei Lun ; Xin, Fuxiao ; Dunker, A. ; Uversky, Vladimir N. ; Radivojac, Predrag. / The structural and functional signatures of proteins that undergo multiple events of post-translational modification. In: Protein Science. 2014 ; Vol. 23, No. 8. pp. 1077-1093.
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