title: Structural insights into BMP receptors: Specificity, activation and inhibition.
abstract: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β family (TGFβ), which signal through hetero-tetrameric complexes of type I and type II receptors. In humans there are many more TGFβ ligands than receptors, leading to the question of how particular ligands can initiate specific signaling responses. Here we review structural features of the ligands and receptors that contribute to this specificity. Ligand activity is determined by receptor-ligand interactions, growth factor prodomains, extracellular modulator proteins, receptor assembly and phosphorylation of intracellular signaling proteins, including Smad transcription factors. Detailed knowledge about the receptors has enabled the development of BMP-specific type I receptor kinase inhibitors. In future these may help to treat human diseases such as fibrodysplasia ossificans progressiva.
authors.affiliation: Institute for Chemistry and Biochemistry, Free University Berlin, Institute of Chemistry and Biochemistry, D-14195 Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité Campus Virchow Klinikum, Augustenburger Platz 1, D-13351 Berlin, Germany. Electronic address: david.yadin@fu-berlin.de.
authors.forename: David
authors.initials: D
authors.lastname: Yadin
authors.affiliation: Institute for Chemistry and Biochemistry, Free University Berlin, Institute of Chemistry and Biochemistry, D-14195 Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité Campus Virchow Klinikum, Augustenburger Platz 1, D-13351 Berlin, Germany. Electronic address: knaus@chemie.fu-berlin.de.
authors.forename: Petra
authors.initials: P
authors.lastname: Knaus
authors.affiliation: Molecular Plant Physiology and Biophysics, Julius-von-Sachs-Institute of the University Wuerzburg, Julius-von-Sachs-Platz 2, D-97082 Wuerzburg, Germany. Electronic address: mueller@biozentrum.uni-wuerzburg.de.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Mueller
mesh_terms: D000818:Animals; D052004:Bone Morphogenetic Protein Receptors / Q000737:chemistry / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009221:Myositis Ossificans / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D019485:Bone Morphogenetic Proteins; D051785:Smad Proteins; D052004:Bone Morphogenetic Protein Receptors
keywords: BMP receptor activation; BMP receptor kinases and inhibitors; Ligand–receptor interaction; Ligand–receptor promiscuity; Protein–protein recognition