Repulsive guidance molecule (RGM) family proteins exhibit differential binding kinetics for bone morphogenetic proteins (BMPs).
Repulsive guidance molecule (RGM) family proteins exhibit differential binding kinetics for bone morphogenetic proteins (BMPs).
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DOI：
10.1371/journal.pone.0046307
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Babitt JL
中科院分区：
文献类型：
--
作者：
Wu Q;Sun CC;Lin HY;Babitt JL
骨形态发生蛋白（BMP）是转化生长因子β超家族的成员，其通过I型和II型丝氨酸苏氨酸激酶受体和SMAD细胞内信号传导途径发挥作用以调节多种生物过程。最近，我们发现，排斥性导向分子（RGM）家族，包括RGMA，RGMB，和RGMC/hemojuvelin（HJV），作为共受体，增强细胞对BMP配体的反应。在这里，我们使用表面等离子体共振定量的BMP配体的RGM蛋白的结合动力学。我们发现，在RGMs中，HJV对BMP 6、BMP 5和BMP 7表现出最高的亲和力，KD分别为8.1、17和20 nM，而对RGMB为28、33和166 nM，对RGMA为55、83和63 nM。相反，RGMB表现出与BMP 4和BMP 2的优先结合，KD分别为2.6和5.5 nM，而HJV为4.5和9.4 nM，RGMA为14和22 nM，而RGMA对大多数测试的BMP表现出最低的结合亲和力。在BMP配体中，RGMs表现出对BMP 4的最高相对亲和力和对BMP 7的最低相对亲和力，而没有RGMs与BMP 9结合。因此，RGMs表现出对BMP配体的不同子集的优先结合。HJV对BMP 6的优先结合与HJV和BMP 6在调节全身铁稳态中的功能作用一致。我们的数据可能有助于解释骨形成蛋白通过有限数量的I型和II型受体发挥细胞环境特异性作用的机制。
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta superfamily that exert their effects via type I and type II serine threonine kinase receptors and the SMAD intracellular signaling pathway to regulate diverse biologic processes. Recently, we discovered that the repulsive guidance molecule (RGM) family, including RGMA, RGMB, and RGMC/hemojuvelin (HJV), function as co-receptors that enhance cellular responses to BMP ligands. Here, we use surface plasmon resonance to quantitate the binding kinetics of RGM proteins for BMP ligands. We show that among the RGMs, HJV exhibits the highest affinity for BMP6, BMP5, and BMP7 with KD 8.1, 17, and 20 nM respectively, versus 28, 33, and 166 nM for RGMB, and 55, 83, and 63 nM for RGMA. Conversely, RGMB exhibits preferential binding to BMP4 and BMP2 with KD 2.6 and 5.5 nM respectively, versus 4.5 and 9.4 nM for HJV, and 14 and 22 nM for RGMA, while RGMA exhibits the lowest binding affinity for most BMPs tested. Among the BMP ligands, RGMs exhibit the highest relative affinity for BMP4 and the lowest relative affinity for BMP7, while none of the RGMs bind to BMP9. Thus, RGMs exhibit preferential binding for distinct subsets of BMP ligands. The preferential binding of HJV for BMP6 is consistent with the functional role of HJV and BMP6 in regulating systemic iron homeostasis. Our data may help explain the mechanism by which BMPs exert cell-context specific effects via a limited number of type I and type II receptors.
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影响因子：
13
作者：
Corradini, Elena;Babitt, Jodie L.;Lin, Herbert Y.
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影响因子：
29.4
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