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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 DOI10.2210/pdb6sf2/pdb
Related6SF1 6SF3
DescriptorSerine/threonine-protein kinase receptor R3, Growth/differentiation factor 2, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
Functional Keywordsbmp9, alk1, prodomain, ternary complex, signalling, tgfbeta, bmp, cytokine
Biological sourceHomo sapiens (Human)
More
Total number of polymer chains6
Total formula weight112434.24
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 citationSalmon, 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: 32238803
DOI: 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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数据于2024-11-06公开中

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