Conservation of the YTH domain at the structural level.

Three left panels, AlphaFold-predicted [74,75] apo structures of YTH domains of Arabidopsis thaliana (Ath) ECT1/9/11 in comparison to that of Ath ECT2, and of Homo sapiens (Hs) YTHDF1. Red/blue coloring in the left-most panel indicates the electrostatic potential of the surface calculated using the APBS PyMOL plugin [131] with the parameters described in Methods. The two middle panels show the similarity of the secondary structure of all proteins and highlight the few non-conservative amino acid substitutions identified in Ath ECT1/9/11 (S16 Fig). Right panel, hydrophobic cage of the same proteins modelled on the crystal structure of the YTH domain of Hs YTHDF1 in complex with RNA GGm6ACU [61] (Protein Data Bank entry 4RCJ). The key residues for m6A binding are marked, including the aspartic to asparagine substitution in the DF-B clade member Ath ECT9 (N342). (PDF)