The BMP7/ActRII extracellular domain complex provides new insights into the cooperative nature of receptor assembly
The BMP7/ActRII extracellular domain complex provides new insights into the cooperative nature of receptor assembly
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DOI：
10.1016/s1097-2765(03)00094-7
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发表时间：
2003-03-01
期刊：
影响因子：
16
通讯作者：
Choe, S
中科院分区：
文献类型：
--
作者：
Greenwald, J;Groppe, J;Choe, S
激活素和骨形态发生蛋白（BMPs）通过两对结构相关的I型和II型受体发出信号，引发多种生物反应。在这里，我们报道了BMP7与激活素II型受体的细胞外结构域（ECD）复合物的晶体结构。我们的结构产生了一个引人注目的四受体模型，揭示了I型和II型受体ECDs没有直接联系。然而，我们发现缺乏细胞质结构域的截断受体保留了在细胞膜内协同组装的能力。此外，BMP7对其低亲和力的I型受体ECD的亲和力在其II型受体ECD存在时增加了5倍。综上所述，我们的研究结果提供了一种不依赖于受体-受体接触的配体介导的BMP和激活素受体的协同组装的观点。
Activins and bone morphogenetic proteins (BMPs) elicit diverse biological responses by signaling through two pairs of structurally related type I and type II receptors. Here we report the crystal structure of BMP7 in complex with the extracellular domain (ECD) of the activin type II receptor. Our structure produces a compelling four-receptor model, revealing that the types I and II receptor ECDs make no direct contacts. Nevertheless, we find that truncated receptors lacking their cytoplasmic domain retain the ability to cooperatively assemble in the cell membrane. Also, the affinity of BMP7 for its low-affinity type I receptor ECD increases 5-fold in the presence of its type II receptor ECD. Taken together, our results provide a view of the ligand-mediated cooperative assembly of BMP and activin receptors that does not rely on receptor-receptor contacts.