Crystal structure of recombinant human growth and differentiation factor 5: evidence for interaction of the type I and type II receptor-binding sites.
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.
Schreuder
Herman
H
sanofi-aventis, Industriepark Hoechst, Building G 865, A-65926 Frankfurt, Germany. Herman.Schreuder@sanofi-aventis.com
Liesum
Alexander
A
Pohl
Jens
J
Kruse
Michael
M
Koyama
Masayoshi
M
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D019485:Bone Morphogenetic Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D003198:Computer Simulation; D003460:Crystallization / Q000379:methods; D003461:Crystallography; D055428:Growth Differentiation Factor 5; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D017154:Stromal Cells / Q000378:metabolism; D013329:Structure-Activity Relationship
D019485:Bone Morphogenetic Proteins; C525893:GDF5 protein, human; C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5; D017978:Receptors, Growth Factor; D017346:Protein Serine-Threonine Kinases; C498218:BMPR2 protein, human; C498219:Bmpr2 protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II