4YCI

non-latent pro-bone morphogenetic protein 9

Summary for 4YCI

• Entry DOI: 10.2210/pdb4yci/pdb
• Related: 4YCG
• Descriptor: Bone Morphogenetic Protein 9 Growth Factor Domain, Bone Morphogenetic Protein 9 Prodomain, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: pro-bmp complex, morphogen, transforming growth factor-beta family, cytokine
• Biological source: Mus musculus (Mouse); More
• Cellular location: Secreted: Q9WV56 Q9UK05
• Total number of polymer chains: 4
• Total formula weight: 91955.30

Authors

Mi, L.Z.,Brown, C.T.,Gao, Y.,Tian, Y.,Le, V.,Walz, T.,Springer, T.A. (deposition date: 2015-02-20, release date: 2015-03-04, Last modification date: 2024-10-23)

Primary citation

Mi, L.Z.,Brown, C.T.,Gao, Y.,Tian, Y.,Le, V.Q.,Walz, T.,Springer, T.A.
Structure of bone morphogenetic protein 9 procomplex.
Proc.Natl.Acad.Sci.USA, 112:3710-3715, 2015

PubMed Abstract: Bone morphogenetic proteins (BMPs) belong to the TGF-β family, whose 33 members regulate multiple aspects of morphogenesis. TGF-β 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-β 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-β1. Despite markedly different arm orientations in pro-BMP and pro-TGF-β, 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.

PubMed: 25751889
DOI: 10.1073/pnas.1501303112

Experimental method

X-RAY DIFFRACTION (3.25 Å)