Large-scale discovery and characterization of protein regulatory motifs in eukaryotes

PLoS One. 2010 Dec 29;5(12):e14444. doi: 10.1371/journal.pone.0014444.

Abstract

The increasing ability to generate large-scale, quantitative proteomic data has brought with it the challenge of analyzing such data to discover the sequence elements that underlie systems-level protein behavior. Here we show that short, linear protein motifs can be efficiently recovered from proteome-scale datasets such as sub-cellular localization, molecular function, half-life, and protein abundance data using an information theoretic approach. Using this approach, we have identified many known protein motifs, such as phosphorylation sites and localization signals, and discovered a large number of candidate elements. We estimate that ~80% of these are novel predictions in that they do not match a known motif in both sequence and biological context, suggesting that post-translational regulation of protein behavior is still largely unexplored. These predicted motifs, many of which display preferential association with specific biological pathways and non-random positioning in the linear protein sequence, provide focused hypotheses for experimental validation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Amino Acid Motifs / genetics*
  • Computational Biology / methods
  • Databases, Protein
  • Eukaryota
  • Humans
  • Mitochondria / metabolism
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteome
  • Proteomics / methods*
  • Saccharomyces cerevisiae / metabolism
  • Schizosaccharomyces / metabolism

Substances

  • Proteins
  • Proteome