6SF2
Ternary complex of human bone morphogenetic protein 9 (BMP9) growth factor domain, its prodomain and extracellular domain of activin receptor-like kinase 1 (ALK1).
Summary for 6SF2
Entry DOI | 10.2210/pdb6sf2/pdb |
Related | 6SF1 6SF3 |
Descriptor | Serine/threonine-protein kinase receptor R3, Growth/differentiation factor 2, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
Functional Keywords | bmp9, alk1, prodomain, ternary complex, signalling, tgfbeta, bmp, cytokine |
Biological source | Homo sapiens (Human) More |
Total number of polymer chains | 6 |
Total formula weight | 112434.24 |
Authors | Salmon, R.M.,Guo, J.,Yu, M.,Li, W. (deposition date: 2019-07-31, release date: 2020-04-08, Last modification date: 2024-01-24) |
Primary citation | Salmon, R.M.,Guo, J.,Wood, J.H.,Tong, Z.,Beech, J.S.,Lawera, A.,Yu, M.,Grainger, D.J.,Reckless, J.,Morrell, N.W.,Li, W. Molecular basis of ALK1-mediated signalling by BMP9/BMP10 and their prodomain-bound forms. Nat Commun, 11:1621-1621, 2020 Cited by PubMed Abstract: Activin receptor-like kinase 1 (ALK1)-mediated endothelial cell signalling in response to bone morphogenetic protein 9 (BMP9) and BMP10 is of significant importance in cardiovascular disease and cancer. However, detailed molecular mechanisms of ALK1-mediated signalling remain unclear. Here, we report crystal structures of the BMP10:ALK1 complex at 2.3 Å and the prodomain-bound BMP9:ALK1 complex at 3.3 Å. Structural analyses reveal a tripartite recognition mechanism that defines BMP9 and BMP10 specificity for ALK1, and predict that crossveinless 2 is not an inhibitor of BMP9, which is confirmed by experimental evidence. Introduction of BMP10-specific residues into BMP9 yields BMP10-like ligands with diminished signalling activity in C2C12 cells, validating the tripartite mechanism. The loss of osteogenic signalling in C2C12 does not translate into non-osteogenic activity in vivo and BMP10 also induces bone-formation. Collectively, these data provide insight into ALK1-mediated BMP9 and BMP10 signalling, facilitating therapeutic targeting of this important pathway. PubMed: 32238803DOI: 10.1038/s41467-020-15425-3 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (3.3 Å) |
Structure validation
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