Abstract
The crystal structure of human growth differentiation factor 5 (GDF5) was solved at 2.4A resolution. The structure is very similar to the structure of bone morphogenetic factor 7 (BMP7) and consists of two banana-shaped monomers, linked via a disulfide bridge. The crystal packing of GDF5 is the same as the crystal packing of BMP7. This is highly unusual since only 25-30% of the crystal contacts involve identical residues. Analysis of the crystal packing revealed that residues of the type I receptor epitope are binding to residues of the type II receptor-binding epitope. The fact that for both BMP family members the type I and type II receptor-binding sites interact suggests that the complementary sites on the receptors may interact as well, suggesting a way how preformed receptor heterodimers may form, similar to the preformed receptors observed for the erythropoietin receptor and the BMP2 receptors.
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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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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Bone Morphogenetic Proteins / ultrastructure*
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Computer Simulation
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Crystallization / methods
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Crystallography
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Growth Differentiation Factor 5
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Humans
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Mice
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Models, Molecular*
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Molecular Sequence Data
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Protein Binding
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Protein Conformation
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Protein Serine-Threonine Kinases / chemistry*
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Protein Serine-Threonine Kinases / metabolism
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Receptors, Growth Factor / chemistry*
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Receptors, Growth Factor / metabolism
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Sequence Homology, Amino Acid
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Stromal Cells / metabolism
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Structure-Activity Relationship
Substances
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Bone Morphogenetic Proteins
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GDF5 protein, human
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Gdf5 protein, mouse
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Growth Differentiation Factor 5
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Receptors, Growth Factor
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Protein Serine-Threonine Kinases
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BMPR2 protein, human
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Bmpr2 protein, mouse
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Bone Morphogenetic Protein Receptors, Type I
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Bone Morphogenetic Protein Receptors, Type II