Close encounters of the third kind: disordered domains and the interactions of proteins.

TitleClose encounters of the third kind: disordered domains and the interactions of proteins.
Publication TypeJournal Article
Year of Publication2009
AuthorsTompa, P., M. Fuxreiter, C. J. Oldfield, I. Simon, K. A Dunker, and V. N. Uversky
JournalBioessays
Volume31
Issue3
Pagination328-35
Date Published2009 Mar
ISSN1521-1878
KeywordsAdsorption, Amino Acid Motifs, Animals, Humans, Protein Binding, Protein Folding, Protein Structure, Tertiary, Proteins
Abstract

Protein-protein interactions are thought to be mediated by domains, which are autonomous folding units of proteins. Recently, a second type of interaction has been suggested, mediated by short segments termed linear motifs, which are related to recognition elements of intrinsically disordered regions. Here, we propose a third kind of protein-protein recognition mechanism, mediated by disordered regions longer than 20-30 residues. Bioinformatics predictions and well-characterized examples, such as the kinase-inhibitory domain of Cdk inhibitors and the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 of actin-binding proteins, show that these disordered regions conform to the definition of domains rather than motifs, i.e., they represent functional, evolutionary, and structural units. Their functions are distinct from those of short motifs and ordered domains, and establish a third kind of interaction principle. With these points, we argue that these long disordered regions should be recognized as a distinct class of biologically functional protein domains.

DOI10.1002/bies.200800151
Alternate JournalBioessays
PubMed ID19260013
Grant List067595 / / Wellcome Trust / United Kingdom
R01 GM071714-01A2 / GM / NIGMS NIH HHS / United States
R01 LM007688-01A1 / LM / NLM NIH HHS / United States