Amino acid specific conservation scores on disordered regions.

<p>Position-specific conservation score for each amino acid across the disordered regions of RNA-binding proteins. Negatively charged residues are less conserved, while arginines are more conserved than the average (blue dashed line). However, additional residues are also significantly more conserved than the average. Residues with mean sequence conservation scores significantly higher than that of the overall dataset are darker orange, while significantly less conserved residues are lighter orange.</p

Parameters that are correlated with the number of interacting partners.

<p>In order to test the hypothesis that disorder is favourable for allowing the protein chains to act as molecular scaffolds, we investigated several parameters in correlation with the number of bound partners in RNA-protein complexes. While the number of partners is positively correlated with the area of the interaction interface (A), and slightly with the length of the sequence, it is weakly and negatively correlated with the ratio of disordered residues. All three parameters were normalized.</p

Examples of constrained disorder.

<p>Two examples of 'constrained' disorder, where both the sequence and the disorder feature are conserved. In the RRM domain of splicing factor Tra2-β1 in complex with RNA (A) both the N- and C-termini regions (orange)adopt a folded state and form extensive interface contacts (left side of panel A) with RNA (blue), whereas they are flexible in the free form (right side of panel A). In the case of Hrp1 protein (B) RNA recognition and binding occurs via tandem RRM modules, and the termini along with the inter-domain linker (orange)are also implicated as a key player in the interaction. This linker is flexible in the unbound state, and forms a short alpha-helix when in complex with RNA (blue). At the bottom of panel A and B the respective sequence and disorder conservation profiles are shown.</p

Conservation of sequence and of disorder.

<p>Heat maps of the sequence- and disorder conservation score pairs of each residue in different sets of structures. Each DisCons [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139731#pone.0139731.ref013" target="_blank">13</a>] 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).</p

Disorder content across taxonomic groups.

<p>The two box plots compare the ratios of disordered residues across major taxonomic groups. The Pfam dataset (A) is significantly biased by viral domains which have an outstandingly high, 30% disorder content. The SwissProt dataset (B) is more balanced, where viral (19%) and eukaryotic (21%) RNA-binding proteins have the highest fraction of disordered residues, along with DNA-binding eukaryotic proteins.</p

Fractions of disordered residues.

<p>Box plot of the ratios of disordered residues across three datasets: The Pfam dataset, the PDB dataset and the SwissProt dataset. DNA- (blue) and RNA- (orange) binding proteins/domains are compared to the reference datasets (grey). In all three datasets the RNA-binding proteins/domains have significantly higher disorder content than the reference data.</p