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Close encounters of the third kind: disordered domains and the interactions of proteins
Author(s) -
Tompa Peter,
Fuxreiter Monika,
Oldfield Christopher J.,
Simon Istvan,
Dunker A. Keith,
Uversky Vladimir N.
Publication year - 2009
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.200800151
Subject(s) - intrinsically disordered proteins , computational biology , biology , protein–protein interaction , protein domain , homology (biology) , folding (dsp implementation) , domain (mathematical analysis) , protein structure , protein folding , three domain system , evolutionary biology , genetics , microbiology and biotechnology , biophysics , biochemistry , gene , genome , mathematical analysis , mathematics , engineering , electrical engineering
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.