期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：12
页码：3710-3715
DOI：10.1073/pnas.1501303112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceBone morphogenetic protein (BMP) activity is regulated by prodomains. Here, structures of BMP procomplexes reveal an open-armed conformation. In contrast, the evolutionarily related, latent TGF-{beta}1 procomplex is cross-armed. We propose that in the TGF-{beta} and BMP family, conversion between cross-armed and open-armed conformations may regulate release and activity of the growth factor. 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-{beta}1. Despite markedly different arm orientations in pro-BMP and pro-TGF-{beta
