Abstract
Bone morphogenetic proteins (BMPs) belong to the large transforming growth factor-beta (TGF-beta) superfamily of multifunctional cytokines. BMP-2 can induce ectopic bone and cartilage formation in adult vertebrates and is involved in central steps in early embryonal development in animals. Signaling by these cytokines requires binding of two types of transmembrane serine/threonine receptor kinase chains classified as type I and type II. Here we report the crystal structure of human dimeric BMP-2 in complex with two high affinity BMP receptor IA extracellular domains (BRIAec). The receptor chains 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 reveals the structural basis for discrimination between type I and type II receptors and the variability of receptor-ligand interactions that is seen in BMP-TGF-beta systems.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Binding Sites
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Protein Receptors, Type I
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Bone Morphogenetic Protein Receptors, Type II
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Bone Morphogenetic Proteins / chemistry*
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Bone Morphogenetic Proteins / metabolism*
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Crystallography, X-Ray
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Dimerization
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Disulfides / metabolism
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Epitopes / chemistry
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Epitopes / metabolism
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Humans
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Models, Molecular
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Molecular Sequence Data
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Phenylalanine / metabolism
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Protein Binding
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Protein Serine-Threonine Kinases / chemistry*
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Protein Serine-Threonine Kinases / metabolism*
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Receptors, Growth Factor / chemistry*
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Receptors, Growth Factor / metabolism*
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Receptors, Transforming Growth Factor beta / chemistry
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Receptors, Transforming Growth Factor beta / metabolism
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Sequence Alignment
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Solvents
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Static Electricity
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Structure-Activity Relationship
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Transforming Growth Factor beta / chemistry
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Transforming Growth Factor beta / metabolism
Substances
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BMP2 protein, human
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins
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Disulfides
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Epitopes
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Receptors, Growth Factor
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Receptors, Transforming Growth Factor beta
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Solvents
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Transforming Growth Factor beta
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Phenylalanine
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Protein Serine-Threonine Kinases
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BMPR1A protein, human
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BMPR2 protein, human
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Bone Morphogenetic Protein Receptors, Type I
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Bone Morphogenetic Protein Receptors, Type II