Title | Close encounters of the third kind: disordered domains and the interactions of proteins. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Tompa, P., M. Fuxreiter, C. J. Oldfield, I. Simon, K. A Dunker, and V. N. Uversky |
Journal | Bioessays |
Volume | 31 |
Issue | 3 |
Pagination | 328-35 |
Date Published | 2009 Mar |
ISSN | 1521-1878 |
Keywords | Adsorption, 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. |
DOI | 10.1002/bies.200800151 |
Alternate Journal | Bioessays |
PubMed ID | 19260013 |
Grant List | 067595 / / Wellcome Trust / United Kingdom R01 GM071714-01A2 / GM / NIGMS NIH HHS / United States R01 LM007688-01A1 / LM / NLM NIH HHS / United States |
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