| Structural highlights
Function
BMP10_HUMAN Required for maintaining the proliferative activity of embryonic cardiomyocytes by preventing premature activation of the negative cell cycle regulator CDKN1C/p57KIP and maintaining the required expression levels of cardiogenic factors such as MEF2C and NKX2-5. Acts as a ligand for ACVRL1/ALK1, BMPR1A/ALK3 and BMPR1B/ALK6, leading to activation of SMAD1, SMAD5 and SMAD8 transcription factors. Inhibits endothelial cell migration and growth. May reduce cell migration and cell matrix adhesion in breast cancer cell lines.[1] [2] [3]
Publication Abstract from PubMed
Heterozygous mutations in BMPR2 (bone morphogenetic protein (BMP) receptor type II) cause pulmonary arterial hypertension. BMPRII is a receptor for over 15 BMP ligands, but why BMPR2 mutations cause lung-specific pathology is unknown. To elucidate the molecular basis of BMP:BMPRII interactions, we report crystal structures of binary and ternary BMPRII receptor complexes with BMP10, which contain an ensemble of seven different BMP10:BMPRII 1:1 complexes. BMPRII binds BMP10 at the knuckle epitope, with the A-loop and beta4 strand making BMPRII-specific interactions. The BMPRII binding surface on BMP10 is dynamic, and the affinity is weaker in the ternary complex than in the binary complex. Hydrophobic core and A-loop interactions are important in BMPRII-mediated signalling. Our data reveal how BMPRII is a low affinity receptor, implying that forming a signalling complex requires high concentrations of BMPRII, hence mutations will impact on tissues with highest BMPR2 expression such as the lung vasculature.
Crystal structures of BMPRII extracellular domain in binary and ternary receptor complexes with BMP10.,Guo J, Liu B, Thorikay M, Yu M, Li X, Tong Z, Salmon RM, Read RJ, Ten Dijke P, Morrell NW, Li W Nat Commun. 2022 May 3;13(1):2395. doi: 10.1038/s41467-022-30111-2. PMID:35504921[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mazerbourg S, Sangkuhl K, Luo CW, Sudo S, Klein C, Hsueh AJ. Identification of receptors and signaling pathways for orphan bone morphogenetic protein/growth differentiation factor ligands based on genomic analyses. J Biol Chem. 2005 Sep 16;280(37):32122-32. doi: 10.1074/jbc.M504629200. Epub 2005, Jul 27. PMID:16049014 doi:http://dx.doi.org/10.1074/jbc.M504629200
- ↑ David L, Mallet C, Mazerbourg S, Feige JJ, Bailly S. Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells. Blood. 2007 Mar 1;109(5):1953-61. doi: 10.1182/blood-2006-07-034124. Epub 2006, Oct 26. PMID:17068149 doi:http://dx.doi.org/10.1182/blood-2006-07-034124
- ↑ Ye L, Bokobza S, Li J, Moazzam M, Chen J, Mansel RE, Jiang WG. Bone morphogenetic protein-10 (BMP-10) inhibits aggressiveness of breast cancer cells and correlates with poor prognosis in breast cancer. Cancer Sci. 2010 Oct;101(10):2137-44. doi: 10.1111/j.1349-7006.2010.01648.x. Epub, 2010 Jul 1. PMID:20608934 doi:http://dx.doi.org/10.1111/j.1349-7006.2010.01648.x
- ↑ Guo J, Liu B, Thorikay M, Yu M, Li X, Tong Z, Salmon RM, Read RJ, Ten Dijke P, Morrell NW, Li W. Crystal structures of BMPRII extracellular domain in binary and ternary receptor complexes with BMP10. Nat Commun. 2022 May 3;13(1):2395. PMID:35504921 doi:10.1038/s41467-022-30111-2
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