title: Functional Advantages of Conserved Intrinsic Disorder in RNA-Binding Proteins.
abstract: Proteins form large macromolecular assemblies with RNA that govern essential molecular processes. RNA-binding proteins have often been associated with conformational flexibility, yet the extent and functional implications of their intrinsic disorder have never been fully assessed. Here, through large-scale analysis of comprehensive protein sequence and structure datasets we demonstrate the prevalence of intrinsic structural disorder in RNA-binding proteins and domains. We addressed their functionality through a quantitative description of the evolutionary conservation of disordered segments involved in binding, and investigated the structural implications of flexibility in terms of conformational stability and interface formation. We conclude that the functional role of intrinsically disordered protein segments in RNA-binding is two-fold: first, these regions establish extended, conserved electrostatic interfaces with RNAs via induced fit. Second, conformational flexibility enables them to target different RNA partners, providing multi-functionality, while also ensuring specificity. These findings emphasize the functional importance of intrinsically disordered regions in RNA-binding proteins.
authors.affiliation: Structural Biology Research Center (SBRC), Flemish Institute of Biotechnology (VIB), Brussels, Belgium; Structural Biology Brussel (SBB), Vrije Universiteit Brussel (VUB), Brussels, Belgium.
authors.forename: Mihaly
authors.initials: M
authors.lastname: Varadi
authors.affiliation: Structural Biology Research Center (SBRC), Flemish Institute of Biotechnology (VIB), Brussels, Belgium; Structural Biology Brussel (SBB), Vrije Universiteit Brussel (VUB), Brussels, Belgium.
authors.forename: Fruzsina
authors.initials: F
authors.lastname: Zsolyomi
authors.affiliation: Structural Biology Research Center (SBRC), Flemish Institute of Biotechnology (VIB), Brussels, Belgium; Structural Biology Brussel (SBB), Vrije Universiteit Brussel (VUB), Brussels, Belgium.
authors.forename: Mainak
authors.initials: M
authors.lastname: Guharoy
authors.affiliation: Structural Biology Research Center (SBRC), Flemish Institute of Biotechnology (VIB), Brussels, Belgium; Structural Biology Brussel (SBB), Vrije Universiteit Brussel (VUB), Brussels, Belgium; Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Tompa
mesh_terms: D000595:Amino Acid Sequence; D008958:Models, Molecular; D011487:Protein Conformation; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D016601:RNA-Binding Proteins