| Structural highlights
Function
[GDF2_MOUSE] Potent circulating inhibitor of angiogenesis. Could be involved in bone formation. Signals through the type I activin receptor ACVRL1 but not other Alks. Signaling through SMAD1 in endothelial cells requires TGF-beta coreceptor endoglin/ENG.[1] [GDF2_HUMAN] Potent circulating inhibitor of angiogenesis. Could be involved in bone formation. Signals through the type I activin receptor ACVRL1 but not other Alks.[2] [3]
Publication Abstract from PubMed
Bone morphogenetic proteins (BMPs) belong to the TGF-beta family, whose 33 members regulate multiple aspects of morphogenesis. TGF-beta family members are secreted as procomplexes containing a small growth factor dimer associated with two larger prodomains. As isolated procomplexes, some members are latent, whereas most are active; what determines these differences is unknown. Here, studies on pro-BMP structures and binding to receptors lead to insights into mechanisms that regulate latency in the TGF-beta family and into the functions of their highly divergent prodomains. The observed open-armed, nonlatent conformation of pro-BMP9 and pro-BMP7 contrasts with the cross-armed, latent conformation of pro-TGF-beta1. Despite markedly different arm orientations in pro-BMP and pro-TGF-beta, the arm domain of the prodomain can similarly associate with the growth factor, whereas prodomain elements N- and C-terminal to the arm associate differently with the growth factor and may compete with one another to regulate latency and stepwise displacement by type I and II receptors. Sequence conservation suggests that pro-BMP9 can adopt both cross-armed and open-armed conformations. We propose that interactors in the matrix stabilize a cross-armed pro-BMP conformation and regulate transition between cross-armed, latent and open-armed, nonlatent pro-BMP conformations.
Structure of bone morphogenetic protein 9 procomplex.,Mi LZ, Brown CT, Gao Y, Tian Y, Le VQ, Walz T, Springer TA Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):3710-5. doi:, 10.1073/pnas.1501303112. Epub 2015 Mar 6. PMID:25751889[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nolan-Stevaux O, Zhong W, Culp S, Shaffer K, Hoover J, Wickramasinghe D, Ruefli-Brasse A. Endoglin requirement for BMP9 signaling in endothelial cells reveals new mechanism of action for selective anti-endoglin antibodies. PLoS One. 2012;7(12):e50920. doi: 10.1371/journal.pone.0050920. Epub 2012 Dec 27. PMID:23300529 doi:http://dx.doi.org/10.1371/journal.pone.0050920
- ↑ David L, Mallet C, Keramidas M, Lamande N, Gasc JM, Dupuis-Girod S, Plauchu H, Feige JJ, Bailly S. Bone morphogenetic protein-9 is a circulating vascular quiescence factor. Circ Res. 2008 Apr 25;102(8):914-22. doi: 10.1161/CIRCRESAHA.107.165530. Epub, 2008 Feb 28. PMID:18309101 doi:10.1161/CIRCRESAHA.107.165530
- ↑ Mahlawat P, Ilangovan U, Biswas T, Sun LZ, Hinck AP. Structure of the Alk1 extracellular domain and characterization of its bone morphogenetic protein (BMP) binding properties. Biochemistry. 2012 Aug 14;51(32):6328-41. Epub 2012 Aug 2. PMID:22799562 doi:10.1021/bi300942x
- ↑ Mi LZ, Brown CT, Gao Y, Tian Y, Le VQ, Walz T, Springer TA. Structure of bone morphogenetic protein 9 procomplex. Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):3710-5. doi:, 10.1073/pnas.1501303112. Epub 2015 Mar 6. PMID:25751889 doi:http://dx.doi.org/10.1073/pnas.1501303112
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