Crystal structure of the BMP-2-BRIA ectodomain complex

Bone morphogenetic proteins (BMPs) belong to the large transforming growth factor-beta (TGF-beta) superfamily of multifunctional cytokines. BMF-2 can induce ectopic bone and cartilage formation in adult vertebrates and is inv olved in central steps in early embryonal development in animals. Signaling by these cytokines requires binding of two types of transmembrane serine/t hreonine receptor kinase chains classified as type I and type II. Here we r eport the crystal structure of human dimeric BMP-2 in complex with two high affinity BMP receptor IA extracellular domains (BRIA(ec)). The receptor ch ains bind to the 'wrist' epitopes of the BMP-2 dimer and contact both BMP-2 monomers, No contacts exist between the receptor domains. The model reveal s the structural basis for discrimination between type I and type II recept ors and the variability of receptor-ligand interactions that is seen in BMP -TGF-beta systems.