Structural studies of the TGF‐βs and their receptors – insights into evolution of the TGF‐β superfamily

TGF-βs are small secreted signaling proteins that function as vital regulators of cellular growth and differentiation. They signal through a single pair of receptors, known as TβR-I and TβR-II, and are among the most recently evolved members of the signaling superfamily to which they belong. This review provides an overview of the TGF-β, BMP, and activin receptor complexes that have been determined over the past several years. These structures underscore the shared ancestry of the TGF-βs with the BMPs and activins, but also provide insight as to how the TGF-βs diverged from the BMPs and activins to bind and assemble their receptors in a distinct manner. These distinctive modes of receptor binding engender the TGF-βs with high specificity for their receptors and allow them to fulfill their essential functions in vivo without interference from the many other proteins of the superfamily.