IBM2 peptide binds to IBD and disrupts menin-MLL-IBD and IN-IBD interactions. (A) HSQC spectrum of 70 µM IBD (black) titrated with 280 μM (blue) and 1 mM (red) IBM2 peptide. (B) Mapping of chemical shift perturbations onto the structure of MLL-IBD complex upon binding of IBM2 peptide. Color coding represents magnitude of chemical shift perturbations: Δσ < 0.025 ppm (yellow), 0.025 < Δσ < 0.08 ppm (orange), and Δσ > 0.08 ppm (red). The MLL fragment is shown in cyan, and the key residues in IBM2 motif are blue. (C) Schematics rationalizing the use of IBM2 peptide as competitor of menin-MLL-IBD and IN-IBD. The IC₅₀ values for competition experiments using IBM2 with menin-MLL-IBD and IN-IBD are shown, respectively, in panels D and E.