Figure 5.

Organization and structures of the type I and type II receptors. (A) A schematic diagram showing the organization of the type I and II receptors. The type I receptor contains a GS motif that is phosphorylated by the type II receptor on serine residues, leading to its activation. The amino acid sequence of the GS loop containing the serine residues that are phosphorylated is shown above the GS motif. The numbering corresponds to amino acid residues in UniProtKB accession numbers Q04771 (human ALK2) and Q13705 (human ActR2B). ECD: extracellular domain; TM: transmembrane. (B, C) Structures of the ALK3 ECD in solution (B) and bound to the BMP-2 ECD (C). The dashed red oval shows that the alpha helix in ALK3 involved in binding BMP-2 is not present in the unbound state. (D, E) Structures of an inactive type I receptor kinase domain (ALK2) (D) and an active type II receptor kinase domain (ActR2B) (E). The GS motif in ALK2 is indicated by the red dashed oval; it interacts with FKBP12 as shown. The GS motif is composed of two alpha helices connected by a loop (yellow) which contain the serine residues that are phosphorylated by the type II receptor. ALK2 contains a salt bridge between residue R375 and residues D336 and D354. Both aspartate residues are required in all kinases for Mg-ATP binding and catalysis. PDB files used to generate the structures are indicated.