Protein disorder and short conserved motifs in disordered regions are enriched near the cytoplasmic side of single-pass transmembrane proteins

PLoS One. 2012;7(9):e44389. doi: 10.1371/journal.pone.0044389. Epub 2012 Sep 4.

Abstract

Intracellular juxtamembrane regions of transmembrane proteins play pivotal roles in cell signalling, mediated by protein-protein interactions. Disordered protein regions, and short conserved motifs within them, are emerging as key determinants of many such interactions. Here, we investigated whether disorder and conserved motifs are enriched in the juxtamembrane area of human single-pass transmembrane proteins. Conserved motifs were defined as short disordered regions that were much more conserved than the adjacent disordered residues. Human single-pass proteins had higher mean disorder in their cytoplasmic segments than their extracellular parts. Some, but not all, of this effect reflected the shorter length of the cytoplasmic tail. A peak of cytoplasmic disorder was seen at around 30 residues from the membrane. We noted a significant increase in the incidence of conserved motifs within the disordered regions at the same location, even after correcting for the extent of disorder. We conclude that elevated disorder within the cytoplasmic tail of many transmembrane proteins is likely to be associated with enrichment for signalling interactions mediated by conserved short motifs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Cell Membrane / chemistry*
  • Cell Membrane / genetics
  • Conserved Sequence
  • Cytoplasm / chemistry*
  • Cytoplasm / genetics
  • Evolution, Molecular
  • Humans
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Molecular Sequence Data
  • Protein Folding
  • Protein Structure, Tertiary
  • Proteomics
  • Sequence Alignment
  • Sequence Homology, Amino Acid

Substances

  • Membrane Proteins

Grants and funding

This work was funded by the Irish Research Council for Science, Engineering and Technology (IRCSET) Graduate Education Research Programme (http://bioinformatics.ucd.ie/PhD), and by Science Foundation Ireland (PI 08/IN.1/B1864). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.