Figure 3. FUS prion-like domain prediction.

The top panel shows the domain architecture of FUS. QGSY-rich=Glutamine, glycine, serine and tyrosine-rich domain; RRM=RNA-recognition motif; G-rich=Glycine-rich domain; RRM=RNA-recognition motif; RGG=RGG domain, a domain with repeated Gly-Gly dipeptides interspersed with Arg and aromatic residues. Zn=Zinc finger motif. Below the cartoon the probability of each residue belonging to the Hidden Markov Model state prion domain or ‘background’ is plotted; the tracks ‘MAP’ and ‘Vit’ illustrate the Maximum a Posteriori and the Viterbi parses of the protein into the prion domain or non-prion domain (Alberti et al., 2009). The plots in the middle panel show the log-likelihood ratio scores (PrD LLR) from the Alberti et al. algorithm in red (Alberti et al., 2009), the predicted prion propensity (PPP) log-odds ratio scores from the Toombs et al. algorithm in green (Toombs et al., 2010) and FoldIndex scores in grey (Prilusky et al., 2005), each averaged over sliding windows of residues. Note that the curves are rescaled to give similar ranges, and so that negative scores are suggestive of both disorder and prion propensity; the rescaled cutoff corresponding to PPP > 0.05 is indicated by the dashed green line. The lower part of the panel shows the primary sequence of TDP-43. The Alberti prion domain is underlined in red (Alberti et al., 2009), the centers of windows satisfying the disorder and prion propensity criteria of Toombs are underlined in grey and green (Toombs et al., 2010), and the cyan residues represent the centers of regions that satisfy both Toombs criteria as well as the amino acid composition requirement of the Alberti algorithm.