Fig. 7

Structure of BMP2/GDF5 heterodimer and comparison of type 1 receptor binding sites to homodimers. A Structure of BMP2/GDF5 heterodimer (PDBID: 8E3G) as compared to previously published apo structures of BMP2 (PDBID: 6OMN) and GDF5 (PDBID: 1WAQ) [46, 63]. BMP2 monomer in blue, GDF5 monomer in green. B Differences in finger orientation of the BMP2 (Top panel) and GDF5 (Bottom panel) monomers in the heterodimer structure (purple) when compared to their respective homodimeric structures (BMP2 in blue, GDF5 in green) as determined by the DynDom server [64]. Flexible hinge point residues shown in red with the axis of rotation in black. Distance from dimerization cysteine to hinge is annotated in the lower panel of each comparison (gray). C Multisequence alignment of the mature domains of human BMP2, BMP4, and GDF5, performed using ClustalOmega [65]. Residues that form hydrogen bonds with type 2 receptors, as determined by PISA analysis of structure of BMP2:Alk3:ActRIIa highlighted in orange (PDBID: 2GOO) [66]. Residues that form hydrogen bonds with type 1 receptors, as determined by PISA analysis of structures of BMP2:Alk3 and GDF5:Alk6 highlighted in yellow (PDBIDs: 1REW, 3EVS) [67, 68]. Conserved hydrophobic residues that form hydrophobic interactions with the type 1 receptor highlighted in gray. Single amino acid difference implicated in Alk3 specificity highlighted in red [26]. Heparin-binding residues highlighted in blue. Secondary structure labeled according to the structure of BMP2 (PDBID: 6OMN) [63]