title: Intrinsic disorder in protein interactions: insights from a comprehensive structural analysis.
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.
authors.affiliation: National Center for Biotechnology Information, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Jessica H
authors.initials: JH
authors.lastname: Fong
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Shoemaker
authors.forename: Sergiy O
authors.initials: SO
authors.lastname: Garbuzynskiy
authors.forename: Michail Y
authors.initials: MY
authors.lastname: Lobanov
authors.forename: Oxana V
authors.initials: OV
authors.lastname: Galzitskaya
authors.forename: Anna R
authors.initials: AR
authors.lastname: Panchenko
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D020539:Sequence Analysis, Protein / Q000379:methods*
chemical_list: D011506:Proteins