Extended Data Fig. 3: Comparisons of DMS data to predicted NDUFAF6 structure.

a. Schematic for the calculation of mutational sensitivity. At each residue position, the number of missense substitutions with a fitness ≤ −0.842 (threshold for variants with strong functional impact, see Extended Data Fig. 2f) are counted and scaled linearly to a value between 0 and 9. b. Mutational sensitivity and percent solvent-accessible surface area (% SASA) of helix 11 (residues 253–275) are shown as bars. A cartoon representation of this alpha helix from the AF6 AlphaFold model is shown below and colored by mutational sensitivity. c. Density plot of DMS fitness scores for proline substitutions grouped by predicted secondary structure. d. Binned scatterplot showing the distribution of percent solvent accessible surface area and mutational sensitivity of residues in AF6. The dot size represents the number of residues in each bin. e. Cartoon representation of the AF6 AlphaFold model colored by mutational sensitivity (top) and % SASA (bottom). A front view and a back view are shown.