Fig. 3: Visualization of the mutations designed for modulating the interaction of FTH1 with NCOA4 and the structure-guided design of the binding site for NCOA4 on FTL.
From: Structural basis for the intracellular regulation of ferritin degradation
a–c NCOA4 is orange, FTH1 is gray, and mutated amino acids are in red, dashed frames designate the presumed position of the amino acids after mutations. a A19Y: abolishes the NCOA4-FTH1 interaction by blocking the opening of the hydrophobic cleft that harbors NCOA4. b N22A: Removes one of the three H-bonds stabilizing the NCOA4-FTH1 interface c R23A: known to abolish the interaction10. R23I and R23L: preserves part of the hydrophobic pocket found in the WT but abolishes the H-bond. d the hydrophobic surface of WT-FTL on the left, WT-FTH1 on the right, and the designed L2H mutant in the middle. The mutations are designated on each panel. Visualization of the phosphomimetic mutations S114D and S114E and a visualization of the designed changes to the electrostatic surface of the gain of function mutant L2H are depicted in Supplementary Figs. 3 and 4, respectively.
