Intrinsic disorder in protein interactions: insights from a comprehensive structural analysis

PLoS Comput Biol. 2009 Mar;5(3):e1000316. doi: 10.1371/journal.pcbi.1000316. Epub 2009 Mar 13.

Abstract

We perform a large-scale study of intrinsically disordered regions in proteins and protein complexes using a non-redundant set of hundreds of different protein complexes. In accordance with the conventional view that folding and binding are coupled, in many of our cases the disorder-to-order transition occurs upon complex formation and can be localized to binding interfaces. Moreover, analysis of disorder in protein complexes depicts a significant fraction of intrinsically disordered regions, with up to one third of all residues being disordered. We find that the disorder in homodimers, especially in symmetrical homodimers, is significantly higher than in heterodimers and offer an explanation for this interesting phenomenon. We argue that the mechanisms of regulation of binding specificity through disordered regions in complexes can be as common as for unbound monomeric proteins. The fascinating diversity of roles of disordered regions in various biological processes and protein oligomeric forms shown in our study may be a subject of future endeavors in this area.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Computer Simulation
  • Models, Chemical*
  • Models, Molecular*
  • Molecular Sequence Data
  • Protein Binding
  • Protein Interaction Mapping / methods*
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteins / ultrastructure*
  • Sequence Analysis, Protein / methods*

Substances

  • Proteins