Fig. 3: The ALK2^KD/BMPR2^KD heterodimer interface localizes to the kinase C-lobes.

a Condensed HDX-MS results comparing isolated BMPR2^KD or ALK2^KD vs. the BMPR2^KD/ALK2^KD complex are mapped to structural models of ALK2^KD (PDB ID: 3H9R) and BMPR2^KD (PDB ID: 3G2F). Complex-induced deuterium exchange perturbations are color-coded according to the scale bar (below) representing the average difference in %D incorporation (Δ%D). Statistical significance was assessed with a two-tailed, unpaired Student’s t test. Regions exhibiting no significant differences in exchange are colored in gray. Regions lacking peptide coverage are noted in white. Complex-induced exchange perturbations mapped to primary sequence are reported in Supplementary Fig. 4. b Deuterium exchange perturbations induced by ALK2^KD/BMPR2^KD complex formation are mapped to the ALK2/BMPR2 C1 kinase dimer model generated by MD simulations. The insets (right) highlight putative interface surfaces. The color-coding scale is the same as in (a). c Zoomed view of the electrostatic interaction network between BMPR2 residue R491, the sidechain of E386, and the backbone carbonyl oxygens of Q403 and Q486. d Detailed view of the complex-induced exchange perturbations centered around helix G of the BMPR2 kinase in the context of the C1 kinase dimer model. Perturbations are color-coded as in (a).