Disordered regions in transmembrane proteins

Gábor E. Tusnády, László Dobson, Peter Tompa

Research output: Contribution to journalArticle

14 Citations (Scopus)


The functions of transmembrane proteins in living cells are widespread; they range from various transport processes to energy production, from cell-cell adhesion to communication. Structurally, they are highly ordered in their membrane-spanning regions, but may contain disordered regions in the cytosolic and extra-cytosolic parts. In this study, we have investigated the disordered regions in transmembrane proteins by a stringent definition of disordered residues on the currently available largest experimental dataset, and show a significant correlation between the spatial distributions of positively charged residues and disordered regions. This finding suggests a new role of disordered regions in transmembrane proteins by providing structural flexibility for stabilizing interactions with negatively charged head groups of the lipid molecules. We also find a preference of structural disorder in the terminal - as opposed to loop - regions in transmembrane proteins, and survey the respective functions involved in recruiting other proteins or mediating allosteric signaling effects. Finally, we critically compare disorder prediction methods on our transmembrane protein set. While there are no major differences between these methods using the usual statistics, such as per residue accuracies, Matthew's correlation coefficients, etc.; substantial differences can be found regarding the spatial distribution of the predicted disordered regions. We conclude that a predictor optimized for transmembrane proteins would be of high value to the field of structural disorder.

Original languageEnglish
Pages (from-to)2839-2848
Number of pages10
JournalBiochimica et Biophysica Acta - Biomembranes
Issue number11
Publication statusPublished - Nov 15 2015


  • Intrinsically disordered residues
  • Positive inside rule
  • Prediction
  • Topology
  • Transmembrane protein

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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