title: Close encounters of the third kind: disordered domains and the interactions of 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.
authors.affiliation: Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest, Hungary. tompa@enzim.hu
authors.forename: Peter
authors.initials: P
authors.lastname: Tompa
authors.forename: Monika
authors.initials: M
authors.lastname: Fuxreiter
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Oldfield
authors.forename: Istvan
authors.initials: I
authors.lastname: Simon
authors.forename: A Keith
authors.initials: AK
authors.lastname: Dunker
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
mesh_terms: D000327:Adsorption; D020816:Amino Acid Motifs; D000818:Animals; D006801:Humans; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011506:Proteins