Fig. 2

3D models for Arg31 substitutions in human BMPR1B. a Structure of the extracellular domain of BMPR1B (green) bound to GDF5 (grey). Position 31 is indicated with the C-atoms colored in magenta. b Model of the BMPR1B variant Arg31Cys. The unpaired cysteine residue located in β-strand 1 is highlighted in magenta; the five disulfide bonds formed in BMPR1B WT are shown as yellow sticks and are marked accordingly. c As in (b) but with an alternative disulfide bond network. The close proximity of the introduced cysteine residue at position 31 to the native residues Cys32, Cys47, Cys53, and Cys71 potentially leads to an alternative connectivity, which could then alter the conformation of the loops. If Cys31 connects to Cys47 an alternative non-native disulfide bond between Cys34 and Cys71 might be formed, which alters the conformation of the β1β2-loop important in the recognition and binding of BMP ligands. d Model of the BMPR1B variant Arg31His. The shorter histidine side chain places the hydrogen bond donor and acceptor groups of the imidazole ring in close proximity to Ser48 and Asn100 allowing to form new hydrogen bonds with the latter two residues thereby possibly altering the conformation of β-strand 2 and the β1β2-loop