Analysis of ECT1/9/11 functional regions.

(A) Topology of the YTH domain of Homo sapiens (Hs) YTHDF1 with secondary structure elements drawn in pink [61]. The two grey helices represent the only structural elements outside the YTH domain as defined by Stoilov et al. [8]: α0 immediately upstream, and α4 at the C-terminus of the protein. Superimposed on the diagrams are the non-conservative amino acid substitutions found in Ath ECT1, ECT9 and ECT11 compared to the majority of Ath ECTs (see alignment in S16 Fig). The localization of these amino acids in the predicted 3D structures, predominantly on the surface, and the spatial integrity of the aromatic cage in the homology models of ECT1/9/11, can be found in S17 Fig. (B) Slab simulations of the IDRs of the indicated proteins showing their tendency to remain in condensed phase or disperse in solution. Source videos of ECT2, ECT1 and ECT11 simulations are provided as S1–S3 Movies (C) Time-averaged density profiles for a subset of the proteins in B. The analyses of the remaining Ath ECTs are shown in S19A Fig. (D) Calculated free energy change for the transition between aqueous solution and condensed phase (ΔGtrans = RT ln [cdilute / cdense]) for the IDRs of the indicated proteins. (E) Cumulative charge distribution of the IDRs of the indicated proteins. The length in amino acids (aa) is at scale. The same analysis for all Ath ECTs can be found in S19D Fig.