Limits...
Functional Advantages of Conserved Intrinsic Disorder in RNA-Binding Proteins.

Varadi M, Zsolyomi F, Guharoy M, Tompa P - PLoS ONE (2015)

Bottom Line: 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.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.These findings emphasize the functional importance of intrinsically disordered regions in RNA-binding proteins.

View Article: PubMed Central - PubMed

Affiliation: Structural Biology Research Center (SBRC), Flemish Institute of Biotechnology (VIB), Brussels, Belgium; Structural Biology Brussel (SBB), Vrije Universiteit Brussel (VUB), Brussels, Belgium.

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.

No MeSH data available.


Related in: MedlinePlus

Conservation of sequence and of disorder.Heat maps of the sequence- and disorder conservation score pairs of each residue in different sets of structures. Each DisCons [13] score pair corresponds to a specific position in a multiple sequence alignment. The score pairs are binned, and the bins are colour coded: from light orange (few) to dark blue (many). Disorder is more conserved in RNA-binding protein chain (C) and especially in the RNA-binding interface residues (D) than in protein- or DNA-binding protein chains (A and B respectively).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4595337&req=5

pone.0139731.g003: Conservation of sequence and of disorder.Heat maps of the sequence- and disorder conservation score pairs of each residue in different sets of structures. Each DisCons [13] score pair corresponds to a specific position in a multiple sequence alignment. The score pairs are binned, and the bins are colour coded: from light orange (few) to dark blue (many). Disorder is more conserved in RNA-binding protein chain (C) and especially in the RNA-binding interface residues (D) than in protein- or DNA-binding protein chains (A and B respectively).

Mentions: The conservation of an important feature, such as the amino acid sequence of a protein, or the presence of intrinsic disorder may help identify functionally important protein segments. We have used our recently developed disorder conservation analysis pipeline, DisCons[13], to quantify the conservation of sequence and of disorder in an evolutionary context. Following the nomenclature of Bellay et al.[14], DisCons classifies disordered positions into three relevant categories: i.) 'Constrained', if both disorder propensity and amino acid sequence are conserved; ii.) 'Flexible', if the sequence shows high degree of variability, yet disorder as a feature is conserved; and finally iii.) 'non-conserved', if the disorder of a position is not consistent. First, we analysed the PDB dataset to provide a background against which to quantify the conservation of disorder in RNA-, DNA- and protein-binding proteins. Disorder and sequence conservation score pairs of each position in the PDB dataset are displayed on Fig 3.


Functional Advantages of Conserved Intrinsic Disorder in RNA-Binding Proteins.

Varadi M, Zsolyomi F, Guharoy M, Tompa P - PLoS ONE (2015)

Conservation of sequence and of disorder.Heat maps of the sequence- and disorder conservation score pairs of each residue in different sets of structures. Each DisCons [13] score pair corresponds to a specific position in a multiple sequence alignment. The score pairs are binned, and the bins are colour coded: from light orange (few) to dark blue (many). Disorder is more conserved in RNA-binding protein chain (C) and especially in the RNA-binding interface residues (D) than in protein- or DNA-binding protein chains (A and B respectively).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4595337&req=5

pone.0139731.g003: Conservation of sequence and of disorder.Heat maps of the sequence- and disorder conservation score pairs of each residue in different sets of structures. Each DisCons [13] score pair corresponds to a specific position in a multiple sequence alignment. The score pairs are binned, and the bins are colour coded: from light orange (few) to dark blue (many). Disorder is more conserved in RNA-binding protein chain (C) and especially in the RNA-binding interface residues (D) than in protein- or DNA-binding protein chains (A and B respectively).
Mentions: The conservation of an important feature, such as the amino acid sequence of a protein, or the presence of intrinsic disorder may help identify functionally important protein segments. We have used our recently developed disorder conservation analysis pipeline, DisCons[13], to quantify the conservation of sequence and of disorder in an evolutionary context. Following the nomenclature of Bellay et al.[14], DisCons classifies disordered positions into three relevant categories: i.) 'Constrained', if both disorder propensity and amino acid sequence are conserved; ii.) 'Flexible', if the sequence shows high degree of variability, yet disorder as a feature is conserved; and finally iii.) 'non-conserved', if the disorder of a position is not consistent. First, we analysed the PDB dataset to provide a background against which to quantify the conservation of disorder in RNA-, DNA- and protein-binding proteins. Disorder and sequence conservation score pairs of each position in the PDB dataset are displayed on Fig 3.

Bottom Line: 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.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.These findings emphasize the functional importance of intrinsically disordered regions in RNA-binding proteins.

View Article: PubMed Central - PubMed

Affiliation: Structural Biology Research Center (SBRC), Flemish Institute of Biotechnology (VIB), Brussels, Belgium; Structural Biology Brussel (SBB), Vrije Universiteit Brussel (VUB), Brussels, Belgium.

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.

No MeSH data available.


Related in: MedlinePlus