Figure 5

Binding epitopes of BMPs and activin for interaction with activin receptors are very similar. (a) Structure based sequence alignment for the regions of BMP-2, BMP-7 and Act-A building the knuckle epitope. The putative contact residues based on the BMP-2:ActR-IIB interaction are color coded according to Fig. 4b. Asterisks mark the amino acid positions chosen for „domain swapping" between BMP-2 and Act-A, the conserved Ser is indicated by a triangle. (b) Sequence alignment of the extracellular domain of ActR-IIB, ActR-II and BMPR-II, the residues contributing to the binding epitope (based on the BMP-2:ActR-IIB interface of this study) are color coded on amino acid properties as in Fig. 4b. (c-e) Comparison of the structural environment around the central H-bond in the complexes of (c) wildtype BMP-2:BMPR-IA:ActR-IIB, (d) Act-A:ActR-IIB (PDB entry 1S4Y, [42]) and (e) BMP-7:ActR-II (PDB entry 1LX5, [40]).